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1
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Chari A, Bal S, Ailawadhi S, Krishnan A, Patel KK, Berdeja JG, Garfall A, Callander N, Banerjee R, Alsina M, Nooka AK, Dhakal B, Gasparetto C, Costello C. Expert Perspectives on Current Challenges and Emerging Approaches for Multiple Myeloma: Narrative Review of an Inaugural Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2025:S2152-2650(25)00098-9. [PMID: 40175263 DOI: 10.1016/j.clml.2025.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 03/04/2025] [Accepted: 03/09/2025] [Indexed: 04/04/2025]
Abstract
PURPOSE The management of multiple myeloma (MM) is becoming increasingly more complex. The approval of novel treatment approaches provides much-needed opportunities but also raises questions and controversies about how to optimally sequence therapies and select treatments for individual patients. METHODS AND RESULTS A panel of experts assembled to discuss current controversies in the care of patients with MM across the disease continuum. Workshop topics included: management of smoldering MM; treatment selection for transplant-eligible and transplant-ineligible patients; risk assessment and the possibility of risk-adapted treatment; use of measurable residual disease (MRD) as a clinical trial end point and to guide treatment decisions; management of early relapse; management of triple class-refractory MM; treatment sequencing; and novel therapies. CONCLUSION Many controversies remain regarding the management of patients with MM related to risk assessment, treatment selection and sequencing, and the optimal use of current therapies while balancing efficacy, toxicity, patient considerations, and treatment logistics. Ongoing research efforts are needed to further define the optimal use of current therapies and to develop more efficacious therapies for all patients and for particular subset populations with unmet need.
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Affiliation(s)
- Ajai Chari
- Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA.
| | - Susan Bal
- Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL
| | | | - Amrita Krishnan
- Judy and Bernard Briskin Myeloma Center, City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Krina K Patel
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jesus G Berdeja
- The Greco-Hainsworth Tennessee Oncology Centers for Research, Nashville, TN
| | - Alfred Garfall
- Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
| | - Natalie Callander
- Division of Hematology, Oncology and Palliative Care, University of Wisconsin Carbone Cancer Center, Madison, WI
| | - Rahul Banerjee
- Department of Medicine, University of Washington, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
| | - Melissa Alsina
- Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Ajay K Nooka
- Department of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA
| | - Binod Dhakal
- Blood and Marrow Transplant (BMT) and Cellular Therapy, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI
| | - Cristina Gasparetto
- Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University School of Medicine, Durham, NC
| | - Caitlin Costello
- Division of Blood and Marrow Transplantation, Moores Cancer Center, University of California San Diego, La Jolla, CA
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2
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Qi Y, Li H, Qi K, Zhu F, Cheng H, Chen W, Yan Z, Li D, Sang W, Fei X, Gu W, Miao Y, Huang H, Wang Y, Qiu T, Qiao J, Pan B, Shi M, Wang G, Li Z, Zheng J, Xu K, Cao J. Clinical outcomes and microenvironment profiling in relapsed/refractory multiple myeloma patients with extramedullary disease receiving anti-BCMA CAR T-cell-based therapy. Am J Hematol 2024; 99:2286-2295. [PMID: 39194355 DOI: 10.1002/ajh.27469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 07/26/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024]
Abstract
Relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T-cell activities in EMD have yet to be determined; how EMD-specific microenvironment influences the clinical outcomes of CAR T-cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra-osseous EMD were enrolled and treated with combined anti-BCMA and anti-CD19 CAR T-cell therapy from May 2017 to September 2023. Thirty-one patients were included in the study. Overall response occurred in 90.3% of medullary disease and 64.5% of EMD (p = .031). Discrepancies in treatment response were noted between medullary and extramedullary diseases, with EMD exhibiting suboptimal and delayed response, as well as shortened response duration. With a median follow-up of 25.3 months, the median progression-free and overall survival were 5.0 and 9.7 months, respectively. Landmark analysis demonstrated that progression within 6 months post-infusion is strongly associated with an increased risk of death (HR = 4.58; p = .029). Compared with non-EMD patients, patients with EMD showed inferior survival outcomes. Unique CAR-associated local toxicities at EMD were seen in 22.6% patients and correlated with the occurrence and severity of systemic cytokine release syndrome. To the cutoff date, 65% treated patients experienced EMD progression, primarily in the form of BCMA+ progression. The pretherapy EMD immunosuppressive microenvironment, characterized by infiltration of exhausted CD8+ T cells, was associated with inferior clinical outcomes. CAR T cells have therapeutic activity in relapsed/refractory EMD, but the long-term survival benefits may be limited. EMD-specific microenvironment potentially impacts treatment. Further efforts are needed to extend EMD remission and improve long-term outcomes.
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Affiliation(s)
- Yuekun Qi
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Hujun Li
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Kunming Qi
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Feng Zhu
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Hai Cheng
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Wei Chen
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Zhiling Yan
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Depeng Li
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Wei Sang
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Xiaoming Fei
- Department of Hematology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Weiying Gu
- Department of Hematology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Yuqing Miao
- Department of Hematology, The First People's Hospital of Yancheng, Yancheng, China
| | - Hongming Huang
- Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, China
| | - Ying Wang
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Tingting Qiu
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Jianlin Qiao
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Bin Pan
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Ming Shi
- Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, China
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Gang Wang
- Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, China
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Zhenyu Li
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Junnian Zheng
- Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, China
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Kailin Xu
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
| | - Jiang Cao
- Blood Diseases Institute Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiangsu Key Laboratory of Bone Marrow Stem Cells, Xuzhou, China
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Gao J, Dong F, Zhang X, Jing H. Efficacy of the CV‑MED regimen in treating extramedullary involvement of multiple myeloma: A case report. Oncol Lett 2024; 28:612. [PMID: 39525606 PMCID: PMC11544527 DOI: 10.3892/ol.2024.14745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 09/19/2024] [Indexed: 11/16/2024] Open
Abstract
Extramedullary progression of multiple myeloma (MM) is commonly associated with a poor prognosis. However, optimal management strategies have not yet been established for the treatment of extramedullary involvement in MM. The present study reports the case of a 59-year-old female patient with MM who experienced extramedullary progression after two cycles of first-line VRD (bortezomib, lenalidomide and dexamethasone) therapy. The patient achieved remission of the extramedullary lesion following treatment with an innovative CV-MED regimen, which includes chidamide, bortezomib, mitoxantrone hydrochloride liposome, etoposide and dexamethasone. Subsequently, the patient underwent autologous hematopoietic stem cell harvesting and maintenance therapy, and remains in a progression-free survival state. The present case suggests that a chemotherapy regimen incorporating mitoxantrone hydrochloride liposomes, chidamide and bortezomib could be a promising treatment strategy for managing extramedullary involvement in MM.
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Affiliation(s)
- Jinjie Gao
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Fei Dong
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Xu Zhang
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China
| | - Hongmei Jing
- Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing 100191, P.R. China
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Elbahoty MH, Papineni B, Samant RS. Multiple myeloma: clinical characteristics, current therapies and emerging innovative treatments targeting ribosome biogenesis dynamics. Clin Exp Metastasis 2024; 41:829-842. [PMID: 39162964 PMCID: PMC11607061 DOI: 10.1007/s10585-024-10305-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 08/01/2024] [Indexed: 08/21/2024]
Abstract
Multiple myeloma (MM) is a clinical disorder characterized by aberrant plasma cell growth in the bone marrow microenvironment. Globally, the prevalence of MM has been steadily increasing at an alarming rate. In the United States, more than 30,000 cases will be diagnosed in 2024 and it accounts for about 2% of cancer diagnoses and more than 2% of cancer deaths, more than double the worldwide figure. Both symptomatic and active MM are distinguished by uncontrolled plasma cell growth, which results in severe renal impairment, anemia, hypercalcemia, and bone loss. Multiple drugs have been approved by the FDA and are now widely used in clinical practice for MM. Although triplet and quadruplet induction regimens, autologous stem cell transplantation (ASCT), and maintenance treatment are used, MM continues to be an incurable illness characterized by relapses that may occur at various phases of its progression. MM patients with frailty, extramedullary disease, plasma cell leukemia, central nervous system recurrence, functional high risk, and the elderly are among those with the greatest current unmet needs. The high cost of care is an additional challenge. MM cells are highly protein secretary cells and thus are dependent on the activation of certain translation pathways. MM also has a high chance of altering ribosomal protein-encoding genes like MYC mutation. In this article we discuss the importance of ribosome biogenesis in promoting MM and RNA polymerase I inhibition as an upcoming treatment with potential promise for MM patients.
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Affiliation(s)
- Mohamed H Elbahoty
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
- Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Bhavyasree Papineni
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rajeev S Samant
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
- Birmingham VA Medical Center, Birmingham, AL, USA.
- O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
- , WTI 320E, 1824 6th Ave South, Birmingham, AL, 35294, USA.
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5
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Zolnowski D, Karp S, Warncke P, Zinn J, Pannach M, Herbst R, Hänel A, Morgner A, Ibach S, Fricke S, Hänel M. Challenges in the treatment of soft-tissue plasmacytoma: a retrospective analysis of 120 patients with extramedullary multiple myeloma. J Cancer Res Clin Oncol 2024; 150:482. [PMID: 39470843 PMCID: PMC11522042 DOI: 10.1007/s00432-024-05993-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 10/09/2024] [Indexed: 11/01/2024]
Abstract
PURPOSE Despite the development of novel drugs and the widespread use of hematopoietic cell transplantation, the prognosis of patients (pts) with multiple myeloma and extramedullary involvement (soft-tissue plasmacytoma, STP) is rather unfavorable. METHODS A retrospective analysis of 120 pts with STP treated between 2007 and 2022 was performed. The effects of demographic and clinical characteristics on treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS The rate of serological response to first-line STP treatment (at least partial remission) was 67%, and the rate of imaging response was 59%. With a median follow-up of 84.2 months, the median PFS was 10.5 months (primary STP: 20.2 months; secondary STP: 5.8 months), and the median OS was 24.5 months (primary STP: 34.5 months; secondary STP: 12.4 months). Based on the multivariate regression analysis, secondary STP (HRPFS 2.75; HROS 2.63) and organ involvement (HRPFS 1.45; HROS 1.68) were found to be negative prognostic factors of both PFS and OS. In a prognostic model, pts with at least one of these factors had a significantly worse PFS (HRPFS 3.31) and OS (HROS 3.45) than those with none risk factor. CONCLUSION In pts with STP, risk-adapted treatment strategies including immunotherapies and cell therapies are urgently required.
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Affiliation(s)
- Dominik Zolnowski
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Simone Karp
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Paul Warncke
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Jessica Zinn
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Marcel Pannach
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Regina Herbst
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Annette Hänel
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Anke Morgner
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
| | - Stefan Ibach
- X-act-Cologne Clinical Research GmbH, Cologne, Germany
| | - Stephan Fricke
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany
- Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
| | - Mathias Hänel
- Department of Internal Medicine III, Klinikum Chemnitz gGmbH, Chemnitz, Germany.
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Stefanidis K, Yusuf G, Mulita F, Tsalikidis C, Mitsala A, Konstantelou E, Kotsopoulou M, Koletsis E, Pitiakoudis M, Dimopoulos P. Extraosseous Plasmacytomas: A Radiologist's Perspective-A Narrative Review of the Literature. Diagnostics (Basel) 2024; 14:1788. [PMID: 39202276 PMCID: PMC11353327 DOI: 10.3390/diagnostics14161788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/10/2024] [Accepted: 08/12/2024] [Indexed: 09/03/2024] Open
Abstract
Extraosseous plasmacytomas (EPs) are rare neoplasms originating from plasma cells, often associated with multiple myeloma. EPs are classified into three subtypes: extramedullary myeloma, solitary extramedullary plasmacytoma (SEP), and multiple solitary plasmacytomas. They can manifest in various anatomical sites, including the lung, mediastinum, breast, liver, pancreas, stomach, mesentery, kidney, small and large bowel, testis, and soft tissue. Despite their rarity, EPs present a diagnostic challenge due to their non-specific imaging appearances, which can mimic other neoplastic and inflammatory conditions. This review aims to describe the radiographic features of EPs in the chest, abdomen, and pelvis based on a thorough analysis of the existing literature. While imaging plays a crucial role in the detection and characterization of EPs, histological confirmation is necessary to differentiate them from other neoplastic entities. The review underscores the importance of considering EPs in the differential diagnosis, particularly in patients with a history of multiple myeloma. Understanding the imaging characteristics of EPs is essential for accurate diagnosis and appropriate management. Early imaging is crucial in these patients to exclude the possibility of EP, as timely diagnosis can significantly impact patient outcomes.
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Affiliation(s)
| | - Gibran Yusuf
- Radiology Department, King’s College Hospital NHS Foundation Trust, London SE5 9RS, UK;
| | - Francesk Mulita
- Department of Surgery, General University Hospital of Patras, 75000 Patras, Greece
| | - Christos Tsalikidis
- Second Department of Surgery, University General Hospital of Alexandroupolis, Democritus University of Thrace Medical School, 68100 Alexandroupolis, Greece; (C.T.); (A.M.)
| | - Athanasia Mitsala
- Second Department of Surgery, University General Hospital of Alexandroupolis, Democritus University of Thrace Medical School, 68100 Alexandroupolis, Greece; (C.T.); (A.M.)
| | | | - Maria Kotsopoulou
- Haematology Department, Metaxa Cancer Hospital, 18537 Piraeus, Greece;
| | - Efstratios Koletsis
- Department of Cardiothoracic Surgery, General University Hospital of Patras, 75000 Patras, Greece;
| | - Michail Pitiakoudis
- Second Department of Surgery, University General Hospital of Alexandroupolis, Democritus University of Thrace Medical School, 68100 Alexandroupolis, Greece; (C.T.); (A.M.)
| | - Platon Dimopoulos
- Department of Radiology, General University of Patras, 61000 Patras, Greece;
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Shepherd K, Obeng G, Randall C, Kolodney J, Willard M. Unveiling Multiple Myeloma: Actively Bleeding Extramedullary Gastric Myelomas Lead to Diagnosis. ACG Case Rep J 2024; 11:e01449. [PMID: 39040955 PMCID: PMC11262812 DOI: 10.14309/crj.0000000000001449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 06/24/2024] [Indexed: 07/24/2024] Open
Abstract
Multiple myeloma (MM) is a disease of plasma cell replication, leading to a disruption of hematopoiesis, which commonly presents clinically with anemia and fatigue. Extramedullary myelomas are plasma cell collections in bone or soft tissue associated with MM and most often occur later in the disease process. We present a case of a patient with symptomatic anemia with actively bleeding gastric nodules, which were later found to be extramedullary gastric myelomas when pathology demonstrated kappa-restricted plasma cell neoplasms. To confirm the overall diagnosis, a bone marrow biopsy verified the patient had MM.
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Affiliation(s)
- Katherine Shepherd
- Department of Internal Medicine, West Virginia University, Morgantown, WV
| | - George Obeng
- Department of Gastroenterology, West Virginia University, Morgantown, WV
| | - Cara Randall
- Department of Pathology, West Virginia University, Morgantown, WV
| | - Joanna Kolodney
- Department of Hematology and Oncology, West Virginia University, Morgantown, WV
| | - Megan Willard
- Department of Gastroenterology, West Virginia University, Morgantown, WV
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8
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Shi H, Zhang M, Su Y, Liu J, Guo J, Liu M, Ma Q. Anti-BCMA CAR-T therapy for multiple myeloma with extramedullary disease: A case report and review of the literature. Medicine (Baltimore) 2024; 103:e38541. [PMID: 38941416 PMCID: PMC11466130 DOI: 10.1097/md.0000000000038541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/21/2024] [Indexed: 06/30/2024] Open
Abstract
INTRODUCTION Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy. CASE PRESENTATION A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva. DIAGNOSIS Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions. INTERVENTION The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy. RESULTS Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue. CONCLUSION MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.
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Affiliation(s)
- Huihui Shi
- Second Clinical College of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Man Zhang
- Second Clinical College of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Yajing Su
- Second Clinical College of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Jingwen Liu
- Second Clinical College of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Jiayuan Guo
- Second Clinical College of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
| | - Mingxin Liu
- Hrain Biotechnology Co. Ltd., Shanghai, P.R. China
| | - Qiuling Ma
- Second Clinical College of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China
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9
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Wadhera S, Jain A, Mitra S, Malhotra P. Extramedullary relapse of multiple myeloma presenting as space-occupying lesion in liver treated with daratumumab, pomalidomide, dexamethasone and bendamustine. BMJ Case Rep 2024; 17:e257346. [PMID: 38627054 PMCID: PMC11029303 DOI: 10.1136/bcr-2023-257346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2024] Open
Abstract
Extramedullary relapse in patients with multiple myeloma (MM) is often associated with loss of biochemical response and the appearance of measurable residual disease in the bone marrow. Fever is an unusual presenting manifestation of MM. Treatment of extramedullary relapse in patients progressing on proteasome inhibitors, anti-CD38 monoclonal antibodies and immunomodulatory drugs is challenging, as access to chimeric antigen receptor T-cells and bispecific antibodies is limited. We report a case of relapsed MM who presented with fever and hepatic space-occupying lesion mimicking hepatocellular carcinoma. In this case report, we also present our experience of using a novel combination regimen comprising Dara-Pom-Benda-Dexa (daratumumab, pomalidomide, dexamethasone and bendamustine) for relapsed MM.
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Affiliation(s)
- Sarthak Wadhera
- Clinical Hematology and Medical Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Arihant Jain
- Clinical Hematology and Medical Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Suvradeep Mitra
- Pathology(Histopathology), Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pankaj Malhotra
- Clinical Hematology and Medical Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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10
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Zhang J, Zhang R. Megalosplenia as an initial manifestation of multiple myeloma with a novel CYLD gene mutation: A case report and literature review. Medicine (Baltimore) 2024; 103:e37624. [PMID: 38579060 PMCID: PMC10994412 DOI: 10.1097/md.0000000000037624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 02/26/2024] [Indexed: 04/07/2024] Open
Abstract
INTRODUCTION Megalosplenia in newly diagnosed multiple myeloma (MM) is extremely rare, posing diagnostic and therapeutic challenges due to its unusual location and clinical manifestations and lack of optimal therapeutic strategies. CASE PRESENTATION A 65-year-old female who was previously healthy presented with a history of ecchymosis on her right leg accompanied by progressive fatigue for 2 weeks. She was admitted to our center in July 2019 due to thrombocytopenia. The patient presented with megalosplenia, anemia, monoclonal protein (λ-light chain type) in the serum and urine, and 45.6% malignant plasma cells in the bone marrow. Splenectomy was performed due to persistent splenomegaly after 3 cycles of the bortezomib plus dexamethasone regimen, and immunohistochemistry results indicated λ-plasmacytoma of the spleen. The same cytogenetic and molecular abnormalities, including t(14;16), 14q32 amplification, 16q32 amplification, 20q12 amplification, and a novel CYLD gene mutation, were identified using fluorescence in situ hybridization and next-generation sequencing in both bone marrow and spleen samples. Therefore, a diagnosis of MM (λ-light chain type, DS III, ISS III, R-ISS III, high-risk) with spleen infiltration was proposed. The patient did not achieve remission after induction treatment with bortezomib plus lenalidomide and dexamethasone or salvage therapy with daratumumab plus ixazomib and dexamethasone. However, she ultimately did achieve very good partial remission with a regimen of bendamustine plus lenalidomide and dexamethasone. Unfortunately, she died of pneumonia associated with chemotherapy. CONCLUSION To our knowledge, only 8 cases of spleen plasmacytoma at MM diagnosis have been described previously. Extramedullary myeloma patients with spleen involvement at diagnosis are younger and that the condition is usually accompanied by splenic rupture with aggressive clinical features and poor prognosis. Further studies are needed to explore pathogenesis and effective therapies to prolong the survival of such patients.
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Affiliation(s)
- Jinjing Zhang
- Department of Hematology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Rui Zhang
- Department of Hematology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
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Chen D, Chen F, Lu J, Wang L, Yao F, Xu H. Doxorubicin-loaded PEG-CdTe QDs conjugated with anti-CXCR4 mAbs: a novel delivery system for extramedullary multiple myeloma treatment. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2024; 35:6. [PMID: 38244066 PMCID: PMC10799820 DOI: 10.1007/s10856-023-06772-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 12/12/2023] [Indexed: 01/22/2024]
Abstract
Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment.
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Affiliation(s)
- Dangui Chen
- Department of hematology, Anqing Municipal Hospital, Anqing, 246003, People's Republic of China
| | - Fei Chen
- Department of hematology, Anqing Municipal Hospital, Anqing, 246003, People's Republic of China
| | - Jia Lu
- Department of hematology, Anqing Municipal Hospital, Anqing, 246003, People's Republic of China
| | - Lihong Wang
- Department of hematology, Anqing Municipal Hospital, Anqing, 246003, People's Republic of China
| | - Fusheng Yao
- Department of hematology, Anqing Municipal Hospital, Anqing, 246003, People's Republic of China.
| | - Haitao Xu
- Department of hematology, Anqing Municipal Hospital, Anqing, 246003, People's Republic of China.
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De S, Samanta S, Shah M. Plasma Cells Out for a Swim! A Study on Myelomatous Involvement of Effusion Fluid and Cerebrospinal Fluid: A 10-Year Experience from a Tertiary Cancer Center. J Cytol 2024; 42:48-53. [PMID: 40078346 PMCID: PMC11896116 DOI: 10.4103/joc.joc_87_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 01/01/2025] [Accepted: 01/06/2025] [Indexed: 03/14/2025] Open
Abstract
Background Multiple myeloma (MM), a hematological malignancy marked by clonal plasma cells in the bone marrow, occasionally presents with myelomatous effusion-a rare condition with a median survival of <4 months. Central nervous system involvement (CNS-MM), characterized by plasma cell infiltration in the CNS, leptomeninges, or cerebrospinal fluid (CSF), is similarly rare and associated with dismal outcomes. Aims To analyze the plasma cell involvement in body fluids and CSF in plasma cell neoplasms, correlating these findings with treatment strategies and patient outcomes. Materials and Methods This retrospective study was conducted in the Oncopathology Department of a tertiary state cancer institute over 10 years (2013-July 2024). It included cases of plasma cell neoplasms with confirmed involvement of body cavity fluids or CSF. Data reviewed included epidemiological profiles, biochemical and hematological findings, immunohistochemistry results, treatment regimens, and follow-up information. Results A total of 16 cases demonstrated neoplastic plasma cell involvement: 12 cases in pleural fluid and 4 cases in CSF. Of these, nine cases were diagnosed with MM, five cases with plasmacytoma, and two cases with plasma cell leukemia. Treatment included chemotherapy (10 patients), palliative radiotherapy (4 patients), combined palliative radiotherapy and chemotherapy (1 patient), and curative radiotherapy with chemotherapy (1 patient). Despite these interventions, the mean survival was only 2 months. Conclusion Myelomatous involvement of effusion fluids and CSF is associated with a grim prognosis. These findings underscore the urgent need for multidisciplinary research and the development of innovative therapeutic strategies to improve outcomes for these patients.
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Affiliation(s)
- Sayantan De
- Department of Oncopathology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Satarupa Samanta
- Department of Oncopathology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Majal Shah
- Department of Oncopathology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
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13
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Koba Y, Kawata T, Tamekane A, Watanabe M. Circumferential gastric wall thickening as initial presentation of relapsed plasma cell leukemia. Clin Endosc 2024; 57:131-133. [PMID: 37536748 PMCID: PMC10834299 DOI: 10.5946/ce.2022.291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 03/15/2023] [Accepted: 03/20/2023] [Indexed: 08/05/2023] Open
Affiliation(s)
- Yusuke Koba
- Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan
| | - Takahito Kawata
- Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akira Tamekane
- Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan
| | - Mitsumasa Watanabe
- Department of Hematology, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan
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Wang J, Shen N, Shen X, Zhang R, Jin Y, Li J, Chen L. Survival trends and prognostic factors of patients with newly diagnosed multiple myeloma accompanied with extramedullary disease. Ann Med 2023; 55:2281657. [PMID: 38086395 PMCID: PMC10880573 DOI: 10.1080/07853890.2023.2281657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 11/03/2023] [Indexed: 12/18/2023] Open
Abstract
Background: Extramedullary disease (EMD) is an unusual event in patients with MM. This study aimed to assess the prognostic impact of EMD and develop an EMD-based risk model to estimate the survival of patients with newly diagnosed multiple myeloma (NDMM).Methods: A total of 518 patients were enrolled in this study, of which 121 presented with EMD at the initial diagnosis. Patients were divided into non-EMD, extramedullary-bone-related (EM-B) and extramedullary-extraosseous (EM-E) groups. Clinical characteristics were compared using the chi-squared test or Fisher's exact test. Survival curves were plotted using the Kaplan-Meier method, and a nomogram was constructed based on the Cox proportional hazards model.Results: Compared to patients without EMDs, patients with EM-E were younger (p = 0.028), and those with EM-B had less renal damage (p < 0.001). The EM-E group had the worst progression-free survival (PFS) and overall survival (OS). In addition, patients with multiple sites of EMD invasion or high Ki67 expression had poor OS. Lenalidomide-based treatment showed the worst outcome, and autologous stem cell transplantation (ASCT) remarkably improved the survival of patients with EMD. A prognostic model (MM prognostic index, MM-PI) comprising lactate dehydrogenase (LDH), circulating plasma cells (CPC), del(17p), and type of extramedullary involvement was developed, and a 4-factor nomogram.Conclusions: We established a risk model incorporating extramedullary disease that provides accurate and individualized survival estimates for patients with NDMM.
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Affiliation(s)
- Jing Wang
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Na Shen
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xuxing Shen
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Run Zhang
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuanyuan Jin
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianyong Li
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lijuan Chen
- Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Coelho H, Badior M, Pinto P, Ribeiro A, Tavares M. Multiple myeloma relapse as extramedullary plasmacytoma of the penis. Ann Hematol 2023; 102:3649-3651. [PMID: 37747588 DOI: 10.1007/s00277-023-05464-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 09/18/2023] [Indexed: 09/26/2023]
Affiliation(s)
- Henrique Coelho
- Department of Hematology, Centro Hospitalar Vila Nova Gaia, Rua Conceição Fernandes, 4434-502, Vila Nova, Gaia, Portugal
| | - Margarida Badior
- Department of Hematology, Centro Hospitalar Vila Nova Gaia, Rua Conceição Fernandes, 4434-502, Vila Nova, Gaia, Portugal
| | - Pedro Pinto
- Department of Hematology, Centro Hospitalar Vila Nova Gaia, Rua Conceição Fernandes, 4434-502, Vila Nova, Gaia, Portugal
| | - Ana Ribeiro
- Department of Pathology, Centro Hospitalar Vila Nova Gaia, Porto, Portugal
| | - Márcio Tavares
- Department of Hematology, Centro Hospitalar Vila Nova Gaia, Rua Conceição Fernandes, 4434-502, Vila Nova, Gaia, Portugal.
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Singh RB, Singhal S, Sinha S, Cho J, Nguyen AXL, Dhingra LS, Kaur S, Sharma V, Agarwal A. Ocular complications of plasma cell dyscrasias. Eur J Ophthalmol 2023; 33:1786-1800. [PMID: 36760117 PMCID: PMC10472748 DOI: 10.1177/11206721231155974] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 01/21/2023] [Indexed: 02/11/2023]
Abstract
Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.
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Affiliation(s)
- Rohan Bir Singh
- Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
- Department of Ophthalmology, Great Ormond Street Institute of Child Health, University College London, London, UK
- Discipline of Ophthalmology and Visual Sciences, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia
| | - Sachi Singhal
- Department of Internal Medicine, Crozer-Chester Medical Center, Upland, PA, USA
| | - Shruti Sinha
- Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Junsang Cho
- Department of Ophthalmology, Vanderbilt Eye Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Lovedeep Singh Dhingra
- Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA
| | - Snimarjot Kaur
- Department of Pediatrics, Yale-New Haven Hospital, New Haven, CT, USA
| | - Vasudha Sharma
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Aniruddha Agarwal
- Department of Ophthalmology, University of Maastricht, Maastricht, the Netherlands
- Department of Ophthalmology, The Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
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Dunphy K, Bazou D, Henry M, Meleady P, Miettinen JJ, Heckman CA, Dowling P, O’Gorman P. Proteomic and Metabolomic Analysis of Bone Marrow and Plasma from Patients with Extramedullary Multiple Myeloma Identifies Distinct Protein and Metabolite Signatures. Cancers (Basel) 2023; 15:3764. [PMID: 37568580 PMCID: PMC10417544 DOI: 10.3390/cancers15153764] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/19/2023] [Accepted: 07/19/2023] [Indexed: 08/13/2023] Open
Abstract
Multiple myeloma (MM) is an incurable haematological malignancy of plasma cells in the bone marrow. In rare cases, an aggressive form of MM called extramedullary multiple myeloma (EMM) develops, where myeloma cells enter the bloodstream and colonise distal organs or soft tissues. This variant is associated with refractoriness to conventional therapies and a short overall survival. The molecular mechanisms associated with EMM are not yet fully understood. Here, we analysed the proteome of bone marrow mononuclear cells and blood plasma from eight patients (one serial sample) with EMM and eight patients without extramedullary spread. The patients with EMM had a significantly reduced overall survival with a median survival of 19 months. Label-free mass spectrometry revealed 225 proteins with a significant differential abundance between bone marrow mononuclear cells (BMNCs) isolated from patients with MM and EMM. This plasma proteomics analysis identified 22 proteins with a significant differential abundance. Three proteins, namely vascular cell adhesion molecule 1 (VCAM1), pigment epithelium derived factor (PEDF), and hepatocyte growth factor activator (HGFA), were verified as the promising markers of EMM, with the combined protein panel showing excellent accuracy in distinguishing EMM patients from MM patients. Metabolomic analysis revealed a distinct metabolite signature in EMM patient plasma compared to MM patient plasma. The results provide much needed insight into the phenotypic profile of EMM and in identifying promising plasma-derived markers of EMM that may inform novel drug development strategies.
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Affiliation(s)
- Katie Dunphy
- Department of Biology, Maynooth University, W23 F2K8 Kildare, Ireland;
| | - Despina Bazou
- Department of Haematology, Mater Misericordiae University Hospital, D07 AX57 Dublin, Ireland; (D.B.); (P.O.)
| | - Michael Henry
- National Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, Ireland; (M.H.); (P.M.)
| | - Paula Meleady
- National Institute for Cellular Biotechnology, Dublin City University, D09 NR58 Dublin, Ireland; (M.H.); (P.M.)
| | - Juho J. Miettinen
- Institute for Molecular Medicine Finland-FIMM, HiLIFE–Helsinki Institute of Life Science, iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00290 Helsinki, Finland; (J.J.M.); (C.A.H.)
| | - Caroline A. Heckman
- Institute for Molecular Medicine Finland-FIMM, HiLIFE–Helsinki Institute of Life Science, iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, 00290 Helsinki, Finland; (J.J.M.); (C.A.H.)
| | - Paul Dowling
- Department of Biology, Maynooth University, W23 F2K8 Kildare, Ireland;
| | - Peter O’Gorman
- Department of Haematology, Mater Misericordiae University Hospital, D07 AX57 Dublin, Ireland; (D.B.); (P.O.)
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Comparison of clinical characteristics, treatment efficacy and survival in patients with newly diagnosed multiple myeloma with single- versus multi-site extramedullary invasion. J Cancer Res Clin Oncol 2023; 149:995-1006. [PMID: 35212816 DOI: 10.1007/s00432-022-03948-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 02/04/2022] [Indexed: 11/27/2022]
Abstract
PURPOSE We aimed to compare the clinical characteristics, treatment efficacy and survival in patients with newly diagnosed multiple myeloma with single- versus multi-site extramedullary invasion. METHODS A total of 90 extramedullary multiple myeloma (EMM) patients were included. We compared the characteristics, overall remission rates (ORRs) and survival among patients with single-site and multi-site invasions. Comparison was also done regarding extramedullary-bone-related (EM-B) and extramedullary-extraosseous (EM-E) multiple myeloma patients. RESULTS Patients with multi-site invasion had higher LDH (179.0 U/L) than single-site invasion (P = 0.016). Significantly higher LDH was also showed in patients with EM-E (189.4 U/L) than EM-B (P = 0.025). The ORR of patients with single-site invasion (72.1%) was not significantly higher than multi-site invasion (68.2%) (P = 0.690). But the ORR of patients with EM-B was significantly higher than EM-E (78.2 vs. 56.3%, P = 0.031). Among patients with single-site invasion, the multivariate survival analysis showed that PI plus IMiD regimen significantly improved the PFS (P < 0.05). Among patients with multi-site invasion or with EM-B, the multivariate survival analysis confirmed the associations of rISS III with poor PFS and OS (P < 0.05). Among patients with EM-E, plasma cell percentage ≥ 20% was associated with significantly poor PFS and OS (P < 0.05). CONCLUSION rISS stage III was possibly associated with poor survival of EMM patients with multi-site invasion or with EM-B. Plasma cell percentage ≥ 20% was associated with poor survival of EMM patients with EM-E. Comparison should not only be done between single- and multi-site invasions, but also between EM-B and EM-E.
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Bhatt P, Kloock C, Comenzo R. Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse. Curr Oncol 2023; 30:2322-2347. [PMID: 36826140 PMCID: PMC9954856 DOI: 10.3390/curroncol30020179] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 02/10/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patient-related factors to consider. In this broad scoping review of available therapies in relapsed/refractory multiple myeloma (RRMM), we cover the pharmacologic mechanisms underlying active therapies such as immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), monoclonal antibodies (mAbs), traditional chemotherapy, and Venetoclax. We then review the clinical data supporting the use of these therapies, organized based on drug resistance/refractoriness, and the role of autologous stem cell transplant (ASCT). Approaches to special situations during relapse such as renal impairment and extramedullary disease are also covered. Lastly, we look towards the future by briefly reviewing the clinical data supporting the use of chimeric antigen receptor (CAR-T) therapy, bispecific T cell engagers (BITE), and Cereblon E3 Ligase Modulators (CELMoDs).
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Affiliation(s)
- Parva Bhatt
- Correspondence: (P.B.); (R.C.); Tel.: +1-617-636-6454
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Yue X, He D, Zheng G, Yang Y, Han X, Li Y, Zhao Y, Wu W, Chen Q, Zhang E, Cai Z, He J. Analysis of High-Risk Extramedullary Relapse Factors in Newly Diagnosed MM Patients. Cancers (Basel) 2022; 14:cancers14246106. [PMID: 36551591 PMCID: PMC9776506 DOI: 10.3390/cancers14246106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 12/14/2022] Open
Abstract
Extramedullary relapse of multiple myeloma (MM) is often resistant to existing treatments, and has an extremely poor prognosis, but our understanding of extramedullary relapse is still limited. The incidence, clinical characteristics, impact on the prognosis of extramedullary relapse, and the risk factors for extramedullary relapse in NDMM patients were analyzed. Among the 471 NDMM patients, a total of 267 patients had disease relapse during follow-up, including 64 (24.0%) patients with extramedullary relapse. Extramedullary relapse was more common in patients with younger age, IgD subtype, elevated LDH, extensive osteolytic lesions, extramedullary involvement, and spleen enlargement at the time of MM diagnosis. Survival analysis showed that extramedullary relapse patients had significantly worse median OS than patients with relapse but without extramedullary involvement (30.8 months vs. 53.6 months, p = 0.012). Multivariate analysis confirmed that elevated LDH (OR = 2.09, p = 0.023), >2 osteolytic lesions (OR = 3.70, p < 0.001), extramedullary involvement (OR = 3.48, p < 0.001) and spleen enlargement (OR = 2.27, p = 0.011) at the time of MM diagnosis were independent risk factors for extramedullary relapse in NDMM patients. Each of the above four factors was assigned a value of 1 to form the extramedullary relapse prediction score, and the 3-year extramedullary relapse rates of patients in the 0−2 and 3−4 score groups were 9.0 % and 76.7 %, respectively. This study suggested that extramedullary relapse was associated with poor clinical characteristics and poor prognosis in NDMM patients. The extramedullary relapse prediction score model composed of LDH, osteolytic lesions, extramedullary involvement and spleen enlargement has a better ability to predict extramedullary relapse than the existing ISS and R-ISS stages.
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Affiliation(s)
- Xiaoyan Yue
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Department of Hematology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Donghua He
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Gaofeng Zheng
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Yang Yang
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Xiaoyan Han
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Yi Li
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Yi Zhao
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Wenjun Wu
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Qingxiao Chen
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Enfang Zhang
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Zhen Cai
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Institute of Hematology, Zhejiang University, Hangzhou 310003, China
- Zhejiang Laboratory for Systems & Precision Medicine, School of Medicine, Zhejiang University, 1369 West Wenyi Road, Hangzhou 311121, China
- Correspondence: (Z.C.); (J.H.)
| | - Jingsong He
- Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Correspondence: (Z.C.); (J.H.)
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Zhang L, Chen S, Wang W, Wang Y, Liang Y. A prognostic model for patients with primary extramedullary multiple myeloma. Front Cell Dev Biol 2022; 10:1021587. [PMID: 36506092 PMCID: PMC9732373 DOI: 10.3389/fcell.2022.1021587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/14/2022] [Indexed: 11/27/2022] Open
Abstract
Background: Extramedullary disease is a manifestation of multiple myeloma, the prognosis of which remains poor even in the era of novel drugs. Therefore, we aimed to develop a predictive model for patients with primary extramedullary multiple myeloma (EMM). Methods: Clinical and laboratory data of patients diagnosed with primary EMM between July 2007 and July 2021 were collected and analyzed. Univariate and least absolute shrinkage and selection operation Cox regression analyses (LASSO) were used to select prognostic factors for overall survival (OS) to establish a nomogram prognostic model. The performance of the model was evaluated using concordance index which was internally validated by bootstraps with 1,000 resample, area under the curve (AUCs), and calibration curves. Results: 217 patients were included in this retrospective study. Patients with EMM had a higher rate of belonging to the male sex, age >50 years, advanced Durie-Salmon stage III, hypercalcemia, and low hemoglobin level. Compared with patients with bone-related extramedullary disease, those with extraosseous-related extramedullary disease had a higher frequency of advanced Durie-Salmon stage III, lower rate of hypercalcemia, and elevated prothrombin time. The OS and progression-free survival (PFS) of patients with bone-related extramedullary disease were significantly higher than those of patients with extraosseous-related extramedullary disease. After the univariate and LASSO analyses, six prognostic factors, including performance status, number of extramedullary involved sites, β2-microglobulin, lactate dehydrogenase, monocyte-lymphocyte ratio, and prothrombin time, were integrated to establish a nomogram. The model showed robust discrimination with a concordance index (C-index) of 0.775 (95% confidence interval [CI], 0.713-0.836), internally validated with the corrected C-index of 0.756, and excellent performance in time-dependent AUCs compared with other staging systems. The AUCs for 1-, 3-, and 5-year OS were 0.814, 0.744, and 0.832, respectively. The calibration curves exhibited good consistency between the observed and nomogram-predicted OS. The 5-year OS of patients in the high-risk group (23.3%; 95% CI, 13.9%-39.3%) was much worse than that in the low-risk group (73.0%; 95% CI, 62.5%-85.4%; p < 0.001). Conclusion: The nomogram predictive model based on six clinical variables showed good prognostic performance and could better predict individual survival in patients with EMM.
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Affiliation(s)
- Limei Zhang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Shuzhao Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Weida Wang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Yun Wang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China,*Correspondence: Yun Wang, ; Yang Liang,
| | - Yang Liang
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, China,*Correspondence: Yun Wang, ; Yang Liang,
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22
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Li X, Wang W, Zhang X, Liang Y. Multiple myeloma with isolated central nervous system relapse after autologous stem cell transplantation: A case report and review of the literature. Front Oncol 2022; 12:1027585. [PMID: 36505789 PMCID: PMC9732423 DOI: 10.3389/fonc.2022.1027585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 11/07/2022] [Indexed: 11/27/2022] Open
Abstract
Patients with multiple myeloma (MM) rarely present with central nervous system (CNS) involvement as a manifestation of extramedullary disease (EMD), a condition that is associated with poor prognosis. CNS relapse without evidence of systemic involvement is even rarer, and there is no standardized treatment because there are only few case reports. We present a 47-year-old female who was diagnosed with nonsecretory multiple myeloma (NSMM) 9 years previously. She had a complete remission after receiving aggressive therapies, including high-dose chemotherapy and autologous stem cell transplantation (ASCT). However, after 7 years of progression-free survival, she had CNS relapse without evidence of systemic involvement. We switched to a salvage regimen consisting of high-dose methotrexate with lenalidomide. She achieved rapid clinical improvement, with a reduction in cerebrospinal fluid plasmacytosis of more than 80%, and no notable side effects. Our description of this unique case of a patient with MM and isolated CNS relapse after ASCT provides a reference for physicians to provide more appropriate management of these patients. We also reviewed previously reported cases and summarized the outcomes of isolated CNS relapse after ASCT, and discuss the pathogenesis and possible treatment strategies for MM with isolated CNS relapse.
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Al-Ataby H, Al-Tkrit A, Ali S, Seneviratne C, Omballi M. Pleural plasmacytomas in a patient with multiple myeloma relapse. Respir Med Case Rep 2022; 40:101777. [DOI: 10.1016/j.rmcr.2022.101777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 10/08/2022] [Accepted: 11/06/2022] [Indexed: 11/15/2022] Open
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24
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Xia Y, Shi Y, Chen Z, Zhang J, Zhu Y, Guo R, Zhang R, Shi Q, Li J, Chen L. Characteristics and prognostic value of extramedullary chromosomal abnormalities in extramedullary myeloma. Chin Med J (Engl) 2022; 135:2500-2502. [PMID: 36583869 PMCID: PMC9945484 DOI: 10.1097/cm9.0000000000002351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Indexed: 12/31/2022] Open
Affiliation(s)
- Yuan Xia
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Hematology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu 225300, China
| | - Yu Shi
- Department of Hematology, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China
| | - Zhi Chen
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Jue Zhang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Yu Zhu
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Rui Guo
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Run Zhang
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Qinglin Shi
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Jianyong Li
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Lijuan Chen
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Vusqa UT, Asawa P, Fazal S, Samhouri Y. Testicular Plasmacytoma Masking as Epididymo-orchitis in a Known Multiple Myeloma Patient. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:549-552. [PMID: 36060019 PMCID: PMC9425583 DOI: 10.21873/cdp.10140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 06/30/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND/AIM Extramedullary plasmacytoma (EMP) is defined as a localized plasma cell neoplasm that arises in tissues other than the bone. The most common sites of involvement of EMP are the upper airways followed by lymph nodes, gastrointestinal tract, thyroid gland, skin, brain, liver, and lungs. Testicular plasmacytoma has a very rare occurrence with about 70 cases reported in literature to date. CASE REPORT We describe a 52-year-old-male with a diagnosis of multiple myeloma presenting with lytic lesions of the axial skeleton. He had lambda light chain restricted, R-ISS stage II with high risk cytogenetics as he tested positive for t(4;14). He underwent four cycles of cyclophosphamide, bortezomib and dexamethasone followed by auto-peripheral stem cell transplantation. He was kept on ixazomib, lenalidomide and dexamethasone maintenance therapy, but relapsed soon after and was diagnosed with plasmacytoma of the left lung. Therapy was switched to daratumumab, carfilzomib and dexamethasone and the patient received radiation of his left lung. He then developed left painless testicular mass which was treated with six weeks course of antibiotics. However due to persistence of concerning features on scrotal ultrasound post-treatment, the patient underwent radical orchiectomy with pathology coming back positive for plasma cells. CONCLUSION The testes serve as a sanctuary site for hematological malignancies due to the presence of the testicular-blood barrier. Hence, it is imperative to keep a high index of suspicion for testicular plasmacytoma in the right clinical context when evaluating a patient with known multiple myeloma.
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Affiliation(s)
- Urwat Til Vusqa
- Department of Internal Medicine, Allegheny Health Network, Pittsburgh, PA, U.S.A
| | - Palash Asawa
- Department of Internal Medicine, Allegheny Health Network, Pittsburgh, PA, U.S.A
| | - Salman Fazal
- Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA, U.S.A
| | - Yazan Samhouri
- Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA, U.S.A
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Allegra A, Cancemi G, Mirabile G, Tonacci A, Musolino C, Gangemi S. Circulating Tumour Cells, Cell Free DNA and Tumour-Educated Platelets as Reliable Prognostic and Management Biomarkers for the Liquid Biopsy in Multiple Myeloma. Cancers (Basel) 2022; 14:cancers14174136. [PMID: 36077672 PMCID: PMC9454477 DOI: 10.3390/cancers14174136] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/24/2022] [Accepted: 08/25/2022] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Even though the presently employed biomarkers in the detection and management of multiple myeloma are demonstrating encouraging results, the mortality percentage of the malignancy is still elevated. Thus, searching for new diagnostic or prognostic markers is pivotal. Liquid biopsy allows the examination of circulating tumour DNA, cell-free DNA, extracellular RNA, and cell free proteins, which are released into the bloodstream due to the breakdown of tumour cells or exosome delivery. Liquid biopsy can now be applied in clinical practice to diagnose, and monitor multiple myeloma, probably allowing a personalized treatment of the disease. Abstract Liquid biopsy is one of the fastest emerging fields in cancer evaluation. Circulating tumour cells and tumour-originated DNA in plasma have become the new targets for their possible employ in tumour diagnosis, and liquid biopsy can define tumour burden without invasive procedures. Multiple Myeloma, one of the most frequent hematologic tumors, has been the target of therapeutic progresses in the last few years. Bone marrow aspirate is the traditional tool for diagnosis, prognosis, and genetic evaluation in multiple myeloma patients. However, this painful procedure presents a relevant drawback for regular disease examination as it requires an invasive practice. Moreover, new data demonstrated that a sole bone marrow aspirate is incapable of expressing the multifaceted multiple myeloma genetic heterogeneity. In this review, we report the emerging usefulness of the assessment of circulating tumour cells, cell-free DNA, extracellular RNA, cell-free proteins, extracellular vesicles, and tumour-educated platelets to evaluate the changing mutational profile of multiple myeloma, as early markers of disease, reliable predictors of prognosis, and as useful tools to perform less invasive monitoring in multiple myeloma.
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Affiliation(s)
- Alessandro Allegra
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy
- Correspondence:
| | - Gabriella Cancemi
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy
| | - Giuseppe Mirabile
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy
| | - Alessandro Tonacci
- Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), 56124 Pisa, Italy
| | - Caterina Musolino
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
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27
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Lee SB, Park CY, Lee HJ, Hong R, Kim WS, Park SG. Non-secretory multiple myeloma expressed as multiple extramedullary plasmacytoma with an endobronchial lesion mimicking metastatic cancer: A case report. World J Clin Cases 2022; 10:7899-7905. [PMID: 36158506 PMCID: PMC9372843 DOI: 10.12998/wjcc.v10.i22.7899] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 11/26/2021] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-secretory multiple myeloma (MM) is a rare condition that accounts for only 3% of MM cases and is defined by normal serum and urine immunofixation and a normal serum free light chain ratio. Non-secretory MM with multiple extramedullary plasmacytomas derived from endobronchial lesions is extremely rare and can be misdiagnosed as metastasis of solid cancer.
CASE SUMMARY A 36-year-old man presented with progressive facial swelling and nasal congestion with cough. Various imaging studies revealed an endobronchial mass in the left bronchus and a large left maxillary mass with multiple destructive bone metastatic lesions. He initially presented with lung cancer and multiple metastases. However, pathologic reports showed multiple extramedullary plasmacytomas in the left maxilla and the left bronchus. There was no change in the serum and urine monoclonal protein levels, and no abnormalities were observed in laboratory examinations, including hemoglobin, calcium, and creatinine levels. The bone marrow was hypercellular, with 13.49% plasma cells. The patient was diagnosed with non-secretory MM expressed as multiple extramedullary plasmacytomas with endobronchial lesions in a rare location. Radiation therapy for symptomatic lesions with high-dose dexamethasone was started, and the size of the left maxillary sinus lesion dramatically decreased. In the future, chemotherapy will be administered to control lesions in other areas.
CONCLUSION We present a rare case of non-secretory MM with multiple extramedullary plasmacytoma with an endobronchial lesion.
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Affiliation(s)
- Seul Bi Lee
- Department of Hemato-oncology, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Chi Young Park
- Department of Hemato-oncology, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Hee Jeong Lee
- Department of Hemato-oncology, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Ran Hong
- Department of Pathology, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Woo Shin Kim
- Department of Laboratory Medicine, Chosun University Hospital, Gwangju 501-717, South Korea
| | - Sang-Gon Park
- Department of Hemato-oncology, Chosun University Hospital, Gwangju 501-717, South Korea
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Li Y, Sun Z, Qu X. Advances in the treatment of extramedullary disease in multiple myeloma. Transl Oncol 2022; 22:101465. [PMID: 35679743 PMCID: PMC9178475 DOI: 10.1016/j.tranon.2022.101465] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/17/2022] [Accepted: 05/26/2022] [Indexed: 11/30/2022] Open
Abstract
Extramedullary multiple myeloma results in an adverse prognosis. Novel agents such as bortezomib, lenalidomide, pomalidomide, isatuximab and selinexor showed efficacy and were recommended to treat EMD. For EMD at special sites, marizomib has advantages in the treatment of CNS-MM; Daratumumab combining with intrapleural bortezomib administration is active in treating myelomatous pleural effusion. Based on treatment experience of EMD in our department, we summarized treatment approach for EMD. Extramedullary disease (EMD) is characterized by plasma cells outside of bone marrow in multiple myeloma (MM) patients, which results in an adverse prognosis. The cornerstone of treatment consists of combination therapy including proteasome inhibitors, immunomodulatory agents, steroids, followed by consolidative autologous hematopoietic stem cell transplantation in eligible patients. This review summarized the recent advances in the treatment of EMD. Bortezomib based therapy showed efficacy and was recommended to treat EMD. Marizomib had advantages in the treatment of central nervous system-multiple myeloma (CNS-MM) because of its good central nervous system penetrability. Immunomodulatory drugs such as lenalidomide and pomalidomide have been reported to be effective. Isatuximab and selinexor were also active. Based on the treatment experience of EMD in our department, we summarized treatment approach for EMD. However, the benefits of patients with EMD from the new era of novel drugs were limited. Novel drugs combination, monoclonal antibody, molecular targeted therapy, cellular immunotherapy and autologous stem cell transplantation (ASCT) are under investigation. Therapeutic studies and clinical trials specifically target EMD should be conducted. Hopefully, these treatment options for EMD will be demonstrated efficacy in the future.
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Multiple myeloma with central nervous system relapse: a case report. MEMO - MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY 2022. [DOI: 10.1007/s12254-022-00822-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Sammartano V, Cerase A, Venanzi V, Mazzei MA, Vangone BE, Gentili F, Chiarotti I, Bocchia M, Gozzetti A. Central Nervous System Myeloma and Unusual Extramedullary Localizations: Real Life Practical Guidance. Front Oncol 2022; 12:934240. [PMID: 35875104 PMCID: PMC9300839 DOI: 10.3389/fonc.2022.934240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 06/10/2022] [Indexed: 12/22/2022] Open
Abstract
Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM during disease course or even rarer at diagnosis. A difference in the origin, i.e., osteodural or primary dural vs leptomeningeal/intraparenchymal, seems to define two distinct types of intracranial myeloma, with different clinical behavior. CNS-MM may occur also as a presentation of MM. Treatment is still unsatisfactory and many treatments have been reported: chemotherapy, intrathecal therapy, and radiotherapy, with dismal prognosis. Other sites of myeloma localization could be also of interest and deserve description. Because of the rarity and aggressiveness of the disease clinicians are often doubtful on how to treat it since there is no general agreement. Moreover, recent drugs such as the anti CD38 monoclonal antibody, immunomodulatory drugs, and proteasome inhibitors have changed the treatment of patients with MM with a significant improvement in overall response and survival. The role of novel agents in CNS MM management and unusual presentations will be discussed as well as the potential role of other new immunomodulatory drugs and proteasome inhibitors that seem to cross the blood-brain barrier. The purpose of this review is to increase awareness of the clinical unusual presentation and neuroradiological findings, give practical diagnostic advice and treatment options algorithm.
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Affiliation(s)
- Vincenzo Sammartano
- Hematology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
| | - Alfonso Cerase
- Neuroimaging (Diagnostic and Functional Neuroradiology) Unit, Azienda ospedaliero-universitaria Senese, Siena, Italy
| | - Valentina Venanzi
- Hematology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
| | - Maria Antonietta Mazzei
- Department of Medicine, Surgery and Neuroscience, University of Siena and Department of Radiological Sciences, Unit of Diagnostic Imaging, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Beatrice Esposito Vangone
- Hematology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
| | - Francesco Gentili
- Department of Medicine, Surgery and Neuroscience, University of Siena and Department of Radiological Sciences, Unit of Diagnostic Imaging, Azienda Ospedaliera Universitaria Senese, Siena, Italy
| | - Ivano Chiarotti
- Neuroimaging (Diagnostic and Functional Neuroradiology) Unit, Azienda ospedaliero-universitaria Senese, Siena, Italy
| | - Monica Bocchia
- Hematology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
| | - Alessandro Gozzetti
- Hematology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Azienda Ospedaliero Universitaria Senese, Siena, Italy
- *Correspondence: Alessandro Gozzetti,
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31
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Zhao WH, Wang BY, Chen LJ, Fu WJ, Xu J, Liu J, Jin SW, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Zhang H, Bai J, Xu Y, Zhu H, Du J, Jiang H, Fan XH, Li JY, Hou J, Chen Z, Zhang WG, Mi JQ, Chen SJ, He AL. Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). J Hematol Oncol 2022; 15:86. [PMID: 35794616 PMCID: PMC9261106 DOI: 10.1186/s13045-022-01301-8] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 06/03/2022] [Indexed: 02/10/2023] Open
Abstract
Background LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. Methods LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. Results As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. Conclusions The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285. Supplementary Information The online version contains supplementary material available at 10.1186/s13045-022-01301-8.
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Affiliation(s)
- Wan-Hong Zhao
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Bai-Yan Wang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Li-Juan Chen
- Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Wei-Jun Fu
- Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China.,Department of Hematology, School of Medicine, Shanghai Fourth People's Hospital, Tongji University, Shanghai, 200434, China
| | - Jie Xu
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China
| | - Jie Liu
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Shi-Wei Jin
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China
| | - Yin-Xia Chen
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Xing-Mei Cao
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Yun Yang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Yi-Lin Zhang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Fang-Xia Wang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Peng-Yu Zhang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Bo Lei
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Liu-Fang Gu
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Jian-Li Wang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Hui Zhang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Ju Bai
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Yan Xu
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Han Zhu
- Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Juan Du
- Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China
| | - Hua Jiang
- Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China
| | - Xiao-Hu Fan
- Nanjing Legend Biotech Inc., Nanjing, 210000, China
| | - Jian-Yong Li
- Department of Hematology, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Jian Hou
- Department of Hematology, Renji Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Zhu Chen
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China
| | - Wang-Gang Zhang
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China
| | - Jian-Qing Mi
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China.
| | - Sai-Juan Chen
- State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Shanghai Institute of Hematology, Ruijin Hospital Affiliated With Shanghai Jiao Tong University School of Medicine, 197 Rui Jin er Road, Shanghai, 200025, China.
| | - Ai-Li He
- Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West 5th Road, Xi'an, 710004, China. .,Department of Hematology and National-Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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32
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Fotiou D, Gavriatopoulou M, Terpos E, Dimopoulos MA. Pomalidomide- and dexamethasone-based regimens in the treatment of refractory/relapsed multiple myeloma. Ther Adv Hematol 2022; 13:20406207221090089. [PMID: 35585966 PMCID: PMC9109494 DOI: 10.1177/20406207221090089] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 03/09/2022] [Indexed: 11/17/2022] Open
Abstract
Pomalidomide is a potent immunomodulatory agent that is currently a standard of care backbone for the treatment of multiple myeloma (MM) patients in the relapsed/refractory setting after exposure to lenalidomide and a proteasome inhibitor. The present review addresses current knowledge regarding the clinical use of pomalidomide in relapsed myeloma patients. Pomalidomide has direct myeloma cell tumoricidal effects by activating proteasomal degradation of Ikaros and Aiolos transcription factors and also indirect effects by modulation of immune responses, interaction with bone marrow stromal cells, and inhibition of angiogenesis. It is approved by regulatory authorities as doublet combination with dexamethasone but four more triplets are also approved for this setting. Many ongoing trials are evaluating the pomalidomide-dexamethasone backbone with newer anti-myeloma class agents or in quadruplet combinations. Pomalidomide-dexamethasone is currently one of the powerful tools available for use in the relapsed/refractory MM setting. Insights into the synergistic immunomodulatory effects of pomalidomide and other anti-myeloma agents and the mechanisms that overcome clonal resistance will potentially allow targeted use of triplet combinations at each relapse.
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Affiliation(s)
- Despina Fotiou
- Department of Clinical Therapeutics, National
and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, National
and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Terpos
- Department of Clinical Therapeutics, National
and Kapodistrian University of Athens, Athens, Greece
| | - Meletios A. Dimopoulos
- Alexandra Hospital, Department of Clinical
Therapeutics, National and Kapodistrian University of Athens, Vas. Sofias 80
and Lourou 4, 11528, Athens, Greece
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33
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Relapse with plasmacytoma after upfront autologous stem cell transplantation in multiple myeloma. Ann Hematol 2022; 101:1217-1226. [PMID: 35445844 DOI: 10.1007/s00277-022-04776-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 01/25/2022] [Indexed: 11/27/2022]
Abstract
Please present P values consistently.Plasmacytoma has been reported to be associated with a poor prognosis in patients with multiple myeloma (MM). In this study, we evaluated the incidence of relapse with plasmacytoma and survival outcomes after upfront autologous stem cell transplantation (ASCT). This study retrospectively analyzed the data of 303 patients with MM who underwent upfront ASCT between April 2000 and April 2018 at eight institutes in the Republic of Korea. In total, 52 patients (17.1%) had plasmacytoma at MM relapse after upfront ASCT, of whom, 27 had paramedullary plasmacytoma (PMD) and 25 had extramedullary plasmacytoma (EMD). Patients with initial plasmacytoma were more likely to have plasmacytoma at MM relapse than those without initial plasmacytoma (37.1% vs. 11.2%). Over a median follow-up of 66.0 months, patients with plasmacytoma at relapse had significantly inferior overall survival (OS) than those without plasmacytoma (43.9 vs. 100.7 months, P < 0.001), but the OS did not significantly differ between patients with EMD and those with PMD (42.2 vs. 56.6 months, P=0.464). After MM relapse, all patients received salvage therapy, and progression-free survival after relapse was significantly shorter in patients with plasmacytoma than in those without (6.4 vs. 12.4 months, P = 0.007). This study showed that plasmacytoma frequently developed at MM relapse after upfront ASCT in patients with plasmacytoma at the time of diagnosis. Plasmacytoma at relapse was significantly associated with a poor prognosis.
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34
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Raghuram S, Faizal B, Sanjeevan KV, Eapen M, Nair IR, Philip A, Pavithran K. Recurrent extramedullary plasmacytomas without multiple myeloma: A case report with review of the literature. Cancer Treat Res Commun 2022; 31:100550. [PMID: 35358819 DOI: 10.1016/j.ctarc.2022.100550] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 12/14/2021] [Accepted: 03/20/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Extramedullary plasmacytoma (EMP) is an uncommon presentation and usually occurs in conjunction with multiple myeloma (MM). An EMP without developing MM at any point is an extremely rare presentation, and only seven such cases have been reported in the literature to date. PRESENTATION OF CASE We present a case of EMP, who presented with multiple recurrent lesions in rare sites like nasal cavity, testis and skin without the involvement of bone marrow at any point of disease course. He was treated with multiagent chemotherapy (DT-PACE) and continues to be in remission at 29 months post-chemotherapy, which is the longest amongst all the cases reported so far. DISCUSSION AND CONCLUSIONS There are no clearly defined guidelines to treat EMP. Our case had a clinical presentation at very unusual sites and was treated with DT-PACE regimen as against the previous seven reported cases and had the most prolonged period of remission.
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Affiliation(s)
- Saadvik Raghuram
- Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre P.O.AIMS Ponekkara, Kochi-682041, Kerala, India
| | - Bini Faizal
- Department of Otorhinolaryngology, Amrita Institute of Medical Sciences and Research Centre P.O.AIMS Ponekkara, Kochi-682041, Kerala, India
| | - K V Sanjeevan
- Department of Urology, Amrita Institute of Medical Sciences and Research Centre P.O.AIMS Ponekkara, Kochi-682041, Kerala, India
| | - Malini Eapen
- Department of Pathology, Amrita Institute of Medical Sciences and Research Centre P.O.AIMS Ponekkara, Kochi-682041, Kerala, India
| | - Indu R Nair
- Department of Pathology, Amrita Institute of Medical Sciences and Research Centre P.O.AIMS Ponekkara, Kochi-682041, Kerala, India
| | - Arun Philip
- Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre P.O.AIMS Ponekkara, Kochi-682041, Kerala, India
| | - Keechilat Pavithran
- Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre P.O.AIMS Ponekkara, Kochi-682041, Kerala, India.
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35
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Bladé J, Beksac M, Caers J, Jurczyszyn A, von Lilienfeld-Toal M, Moreau P, Rasche L, Rosiñol L, Usmani SZ, Zamagni E, Richardson P. Extramedullary disease in multiple myeloma: a systematic literature review. Blood Cancer J 2022; 12:45. [PMID: 35314675 PMCID: PMC8938478 DOI: 10.1038/s41408-022-00643-3] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 11/26/2021] [Accepted: 03/07/2022] [Indexed: 12/19/2022] Open
Abstract
Extramedullary involvement (or extramedullary disease, EMD) represents an aggressive form of multiple myeloma (MM), characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment. Several different definitions of EMD have been used in the published literature. We advocate that true EMD is restricted to soft-tissue plasmacytomas that arise due to hematogenous spread and have no contact with bony structures. Typical sites of EMD vary according to the phase of MM. At diagnosis, EMD is typically found in skin and soft tissues; at relapse, typical sites involved include liver, kidneys, lymph nodes, central nervous system (CNS), breast, pleura, and pericardium. The reported incidence of EMD varies considerably, and differences in diagnostic approach between studies are likely to contribute to this variability. In patients with newly diagnosed MM, the reported incidence ranges from 0.5% to 4.8%, while in relapsed/refractory MM the reported incidence is 3.4 to 14%. Available data demonstrate that the prognosis is poor, and considerably worse than for MM without soft-tissue plasmacytomas. Among patients with plasmacytomas, those with EMD have poorer outcomes than those with paraskeletal involvement. CNS involvement is rare, but prognosis is even more dismal than for EMD in other locations, particularly if there is leptomeningeal involvement. Available data on treatment outcomes for EMD are derived almost entirely from retrospective studies. Some agents and combinations have shown a degree of efficacy but, as would be expected, this is less than in MM patients with no extramedullary involvement. The paucity of prospective studies makes it difficult to justify strong recommendations for any treatment approach. Prospective data from patients with clearly defined EMD are important for the optimal evaluation of treatment outcomes.
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Affiliation(s)
- Joan Bladé
- Department of Hematology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
| | - Meral Beksac
- Department of Hematology, Ankara University School of Medicine, Ankara, Turkey
| | - Jo Caers
- Department of Hematology, CHU de Liège, Liège, Belgium
| | - Artur Jurczyszyn
- Plasma Cell Dyscrasia Center, Department of Hematology, Jagiellonian University Medical College, Cracow, Poland
| | - Marie von Lilienfeld-Toal
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany
| | | | - Leo Rasche
- Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany
| | - Laura Rosiñol
- Department of Hematology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Saad Z Usmani
- Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Atrium Health, Charlotte, NC, USA
| | - Elena Zamagni
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli' and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy
| | - Paul Richardson
- Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
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36
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Bhalla D, Chandrashekhara SH, Razik A, Sharma A, Giri RK. Walking the Risk-Benefit Tight Rope: A Case of Post Fine Needle Aspiration Haemorrhage in Extramedullary Plasmacytoma. Curr Med Imaging 2022; 18:1012-1015. [PMID: 35260058 DOI: 10.2174/1573405618666220308102941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 12/10/2021] [Accepted: 01/17/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Primary extramedullary plasmacytomas (EMP) are rare, however secondary forms may be seen in ~10-15% patients with systemic multiple myeloma (MM). The diagnosis of EMP is based on demonstration of monoclonal plasma cells in the lesion, which requires tissue sampling. CASE PRESENTATION We present a case of a 38 year old female with MM, who underwent diagnostic US at our institute. Multiple focal liver lesions were detected, which were suspicious for EMP. She underwent fine needle aspiration cytology (FNAC) for diagnosis, following which she developed hemoperitoneum secondary to deranged clotting parameters (prothrombin time and platelet count). CT Angiography revealed active hepatic capsular bleed. She was taken up for percutaneous embolisation, and the supplying vessel successfully embolised using gelfoam particles. Complications may rarely occur in interventional procedures, particularly in patients with comorbidities. However, prompt diagnosis and management help prevent adverse outcomes.
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Affiliation(s)
- Deeksha Bhalla
- Department of Radiodiagnosis, BRA IRCH, All India Institute of Medical Sciences, New Delhi, India
| | - S H Chandrashekhara
- Department of Radiodiagnosis, BRA IRCH, All India Institute of Medical Sciences, New Delhi
| | - Abdul Razik
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Atul Sharma
- Department of Medical Oncology, BRA IRCH, All India Institute of Medical Sciences, New Delhi
| | - Rupak Kumar Giri
- Department of Medical Oncology, BRA IRCH, All India Institute of Medical Sciences, New Delhi
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37
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Hirao M, Yamazaki K, Watanabe K, Mukai K, Hirose S, Osada M, Tsukada Y, Kunieda H, Denda R, Kikuchi T, Sugimori H, Okamoto S, Hattori Y. Negative E-cadherin expression on bone marrow myeloma cell membranes is associated with extramedullary disease. F1000Res 2022. [PMID: 35646332 DOI: 10.5061/dryad.ns1rn8pvn] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background: The loss of E-cadherin expression and the induction of N-cadherin are known as hallmarks of the epithelial-to-mesenchymal transition, an essential initial step in the process of metastasis in solid tumors. Although several studies have reported expressions of these cadherins in patients with multiple myeloma (MM), their clinical significance is unknown as MM cells are non-epithelial. Methods: In this study, we examined the expression of E- and N-cadherins by immunohistochemistry using bone marrow (BM) biopsy specimens from 31 newly diagnosed MM patients and in subsequent biopsy specimens from six of these. Results: Negative E-cadherin expression on BM myeloma cell membranes was significantly associated with the presence of soft-tissue masses arising from bone lesions and breaking through the cortical bone, referred to as extramedullary disease (EMD). Conclusions: Given the aggressive nature of EMD, our study suggests that screening for E-cadherin using BM immunohistochemistry is one measure that could predict the development of EMD in patients with MM.
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Affiliation(s)
- Maki Hirao
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Kohei Yamazaki
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Kentaro Watanabe
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan.,Department of Medicine, Sowa Hospital, 1752 Oshima, Midori-ku, Sagamihara, Kanagawa, 252-0135, Japan
| | - Kiyoshi Mukai
- Department of Diagnostic Pathology, Keiyu Hospital, 3-7-3 Minatomirai, Nishi-ku, Yokohama, Kanagawa, 220-8521, Japan
| | - Shigemichi Hirose
- Department of Diagnostic Pathology, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Makoto Osada
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan.,Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yuiko Tsukada
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Hisako Kunieda
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Ryunosuke Denda
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Takahide Kikuchi
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Hiroki Sugimori
- Department of Preventive Medicine, Daito Bunka University Faculty of Sports and Health Sciences Graduate School of Sports and Health Sciences, 560 Iwadono, Higashimatsuyama, Saitama, 355-8501, Japan
| | - Shinichiro Okamoto
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan
| | - Yutaka Hattori
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo, 108-0073, Japan.,Division of Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy Graduate School of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan
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38
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Li Y, Ji J, Lu H, Li J, Qu X. Pomalidomide-based therapy for extramedullary multiple myeloma. Hematology 2022; 27:88-94. [PMID: 35068387 DOI: 10.1080/16078454.2021.2019364] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Affiliation(s)
- Yating Li
- The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China
| | - Jiamei Ji
- The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China
| | - Hua Lu
- The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China
| | - Jianyong Li
- The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China
| | - Xiaoyan Qu
- The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China
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39
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Halaseh RM, Kaur S, Khanna R, Conkling P, Sarna N, Magee A. Hyperviscosity syndrome in IgA multiple myeloma. QJM 2022; 115:30-31. [PMID: 34191019 DOI: 10.1093/qjmed/hcab175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Indexed: 11/14/2022] Open
Affiliation(s)
- R M Halaseh
- From the Internal Medicine Department, Medstar Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010, USA
| | - S Kaur
- From the Internal Medicine Department, Medstar Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010, USA
| | - R Khanna
- From the Internal Medicine Department, Medstar Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010, USA
| | - P Conkling
- From the Internal Medicine Department, Medstar Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010, USA
| | - N Sarna
- From the Internal Medicine Department, Medstar Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010, USA
| | - A Magee
- From the Internal Medicine Department, Medstar Washington Hospital Center, 110 Irving Street NW, Washington, DC 20010, USA
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40
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Duodenal Ulcer with Massive Gastrointestinal Hemorrhage as an Initial Manifestation in Multiple Myeloma with Extramedullary Disease: A Case Report. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58010134. [PMID: 35056442 PMCID: PMC8780751 DOI: 10.3390/medicina58010134] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 12/24/2022]
Abstract
Plasma cell neoplasms are characterized by dysregulated proliferation of mature B cells, which can present with either single (solitary plasmacytoma) or systemic (multiple myeloma (MM)) involvement. MM with extramedullary plasmacytoma (EMP) is a rare disease that accounts for approximately 3-5% of all plasmacytomas. EMP with gastrointestinal (GI) system involvement is an even rarer entity, accounting for <1% of MM cases. We present a case of aggressive MM with EMP invading the duodenum, initially presented with massive upper GI hemorrhage and small bowel obstruction. A 67-year-old woman was admitted to our hospital owing to a lack of either gas or feces passage for 3 days. Abdominal distention and vomit with a high coffee ground content were observed for 24 h. The patient's condition was initially diagnosed as small bowel obstruction, upper gastrointestinal bleeding, severe anemia, acute renal failure, and hypercalcemia. Furthermore, an analysis of immunoelectrophoresis in the blood, bone marrow aspiration, and tissue biopsy supported the diagnosis of MM and EMP invading the duodenum, upper GI hemorrhage, and small bowel obstruction. Our study provided the possible involvement of MM and EMP in the differential diagnosis of patients with unexplained GI hemorrhage and small bowel obstruction. A thorough review of the literature regarding the association between MM, GI hemorrhage, and small bowel obstruction is presented in this study.
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41
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Gao S, Li Q, Dong F, Yang P, Chen Y, Wang J, Wang Y, Jing H. Clinical characteristics and survival outcomes of newly diagnosed multiple myeloma patients presenting with extramedullary disease: a retrospective study. Leuk Res 2022; 115:106793. [DOI: 10.1016/j.leukres.2022.106793] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/15/2022] [Accepted: 01/25/2022] [Indexed: 10/19/2022]
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42
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Li W, Liu M, Yuan T, Yan L, Cui R, Deng Q. Efficacy and follow-up of humanized anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma patients with extramedullary-extraosseous, extramedullary-bone related, and without extramedullary disease. Hematol Oncol 2021; 40:223-232. [PMID: 34942032 PMCID: PMC9305928 DOI: 10.1002/hon.2958] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 12/04/2021] [Accepted: 12/20/2021] [Indexed: 12/02/2022]
Abstract
The prognosis of patients with multiple myeloma (MM) with extramedullary disease (EMD) remains poor. A high overall response rate (ORR) has been reported following anti‐B‐cell maturation antigen (BCMA) chimeric antigen receptor (CAR)‐T cell therapy in relapsed/refractory (R/R) patients with MM; however, data on patients with EMD remain limited. Herein, we compared and analyzed the efficacy and long‐term follow‐up of anti‐BCMA CAR‐T cell therapy in R/R MM patients with extramedullary‐extraosseous (EM‐E), extramedullary‐bone related (EM‐B), and without extramedullary disease. No difference in the ORR was observed between the three groups. The long‐term efficacy of anti‐BCMA CAR‐T cell therapy in the EM‐E group was worse than that in patients without EMD and with EM‐B. In the EM‐E group, disease progression was the reappearance of extramedullary lesions without an increase in the MM cell percentage or M protein level. Although no difference in the proportion of CAR‐T cells was detected among the three groups, the EM‐E group might exhibit a relatively high grade of cytokine release syndrome following anti‐BCMA CAR‐T therapy. Interleukin‐6 levels in the without EMD group were lower than those in the EM‐E and EM‐B groups. However, given the small number of cases in the three groups, statistical analysis was not performed.(ChiCTR1800017051 and ChiCTR2000033925).
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Affiliation(s)
- Wei Li
- The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Meijing Liu
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Ting Yuan
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Lixiang Yan
- The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rui Cui
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Qi Deng
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
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43
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Manolitsis I, Tzelves L, Koutoulidis V, Gavriatopoulou M, Varkarakis I. Metachronous Bilateral Testicular Plasmacytoma After an Initial Soft Tissue, Extramedullary Plasmacytoma. Cureus 2021; 13:e19517. [PMID: 34934542 PMCID: PMC8666563 DOI: 10.7759/cureus.19517] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2021] [Indexed: 11/25/2022] Open
Abstract
Testicular plasmacytoma is a rare extramedullary manifestation of plasma cell dyscrasia. We report a case of a 53-year-old man who presented with a metachronous testicular lesion originating from a soft tissue plasmacytoma of the oral cavity. He underwent radical orchiectomy and a year later, presented with testicular plasmacytoma in the contralateral testis. He received induction chemotherapy, autologous stem cell transplantation with high dose melphalan and maintenance with lenalidomide, as he refused orchiectomy and achieved complete remission. However, six months post-transplant, he relapsed with localized disease in his testis, received second-line chemotherapy, after refusing orchiectomy and still remains in partial remission and alive.
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Affiliation(s)
- Ioannis Manolitsis
- Second Department of Urology, National and Kapodistrian University of Athens, Sismanogleio General Hospital, Athens, GRC
| | - Lazaros Tzelves
- Second Department of Urology, National and Kapodistrian University of Athens, Sismanogleio General Hospital, Athens, GRC
| | - Vassilis Koutoulidis
- First Department of Radiology, National and Kapodistrian University of Athens, Aretaieion Hospital, Athens, GRC
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Greece, Alexandra General Hospital, Athens, GRC
| | - Ioannis Varkarakis
- Second Department of Urology, National and Kapodistrian University of Athens, Sismanogleio General Hospital, Athens, GRC
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44
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Chen Y, Tao S, Zheng X, Shi Y, Zhang L, Chen K, He Z, Wang C, Yu L. Research progress on treatment of extramedullary multiple myeloma. Hematology 2021; 26:985-994. [PMID: 34871523 DOI: 10.1080/16078454.2021.2005310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
ABSTRACTObjectives: Extramedullary multiple myeloma (EMM) is a relatively less frequent subentity of multiple myeloma (MM) and is generally considered to be a poor prognostic factor. Novel agents and hematopoietic stem cell transplantation (HSCT) have led to a significant improvement in the progression-free survival and overall survival of patients with MM, but outcomes of EMM remain dismal. Little is known regarding the role of novel therapies in this setting. This review summarizes the current available data regarding the roles of proteasome inhibitors, immunomodulators, monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy and HSCT in EMM.Methods: A systematic literature review through PubMed was conducted to summarize the published evidence on the therapeutic developments of novel agents and HSCT in EMM. Literature sources published in English were searched, using the terms multiple myeloma, extramedullary and treatment.Results: Long-term outcomes of EMM patients remain dismal despite the utilization of novel agents and HSCT. The standard therapy of EMM has not been established. EMM should be managed as high-risk disease and treated accordingly.Discussion and conclusion: This review will provide an insight on the current and emerging treatment strategies as well as their efficacy in EMM. Further subgroup analyses in large prospective trials focusing on EMM is needed to help optimize the therapy.
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Affiliation(s)
- Yue Chen
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China
| | - Shandong Tao
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China
| | - Xinqi Zheng
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China
| | - Yuye Shi
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China
| | - Lijuan Zhang
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China
| | - Kankan Chen
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China
| | - Zhengmei He
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China
| | - Chunling Wang
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China.,Key Laboratory of Hematology, Nanjing Medical University, Nanjing, People's Republic of China
| | - Liang Yu
- Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China.,Key Laboratory of Hematology, Nanjing Medical University, Nanjing, People's Republic of China
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45
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Stork M, Sevcikova S, Minarik J, Krhovska P, Radocha J, Pospisilova L, Brozova L, Jarkovsky J, Spicka I, Straub J, Pavlicek P, Jungova A, Jelinek T, Sandecka V, Maisnar V, Hajek R, Pour L. Identification of patients at high risk of secondary extramedullary multiple myeloma development. Br J Haematol 2021; 196:954-962. [PMID: 34726261 PMCID: PMC9297924 DOI: 10.1111/bjh.17925] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 10/14/2021] [Indexed: 12/12/2022]
Abstract
Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4·38, 95% confidence interval (CI): 2·46–7·80, P < 0·0001], high lactate dehydrogenase (LDH) levels (>5 μkat/l; OR 2·07, 95% CI: 1·51–2·84, P < 0·0001), extensive osteolytic activity (OR 2·21, 95% CI: 1·54–3·15, P < 0·001), and immunoglobulin A (IgA; OR 1·53, 95% CI: 1·11–2·11, P = 0·009) or the non‐secretory type of MM (OR 2·83; 95% CI: 1·32–6·04, P = 0·007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression‐free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13·8 months (95% CI: 11·4–16·3) vs 18·8 months (95% CI: 17·7–19·9), P = 0·006; mOS: 26·7 months (95% CI: 18·1–35·4) vs 58·7 months (95% CI: 54·8–62·6), P < 0·001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.
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Affiliation(s)
- Martin Stork
- Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
| | - Sabina Sevcikova
- Babak Myeloma Group, Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Jiri Minarik
- Department of Hemato-Oncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
| | - Petra Krhovska
- Department of Hemato-Oncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
| | - Jakub Radocha
- 4th Department of Internal Medicine - Hematology, Faculty Hospital and Charles University in Hradec Kralove, Hradec Kralove, Czech Republic
| | | | - Lucie Brozova
- Institute of Biostatistics and Analyses, Ltd., Brno, Czech Republic
| | - Jiri Jarkovsky
- Institute of Biostatistics and Analyses, Ltd., Brno, Czech Republic
| | - Ivan Spicka
- 1st Medical Department - Clinical Department of Haematology of the First Faculty of Medicine and General Teaching Hospital Charles University, Prague, Czech Republic
| | - Jan Straub
- Department of Internal Medicine and Hematology, University Hospital Kralovske Vinohrady, Prague, Czech Republic
| | - Petr Pavlicek
- Department of Internal Medicine and Hematology, University Hospital Kralovske Vinohrady, Prague, Czech Republic
| | - Alexandra Jungova
- Hematology and Oncology Department, Charles University Hospital, Pilsen, Czech Republic
| | - Tomas Jelinek
- Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Viera Sandecka
- Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
| | - Vladimir Maisnar
- 4th Department of Internal Medicine - Hematology, Faculty Hospital and Charles University in Hradec Kralove, Hradec Kralove, Czech Republic
| | - Roman Hajek
- Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Ludek Pour
- Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
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46
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Abdallah A, Mohyuddin GR, Ahmed N, Mohan M, Cui W, Shune L, Mahmoudjafari Z, McGuirk J, Ganguly S, Atrash S. Outcomes of VDPACE with an immunomodulatory agent as a salvage therapy in relapsed/refractory multiple myeloma with extramedullary disease. EJHAEM 2021; 2:757-764. [PMID: 35845187 PMCID: PMC9175829 DOI: 10.1002/jha2.275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/25/2021] [Accepted: 07/26/2021] [Indexed: 04/21/2023]
Abstract
Extramedullary disease (EMD) is an aggressive form of multiple myeloma (MM). Confirming the presence of plasma cells outside the bone marrow makes the diagnosis of EMD. There is no clear consensus on the management of EMD in MM, and this entity continues to remain an unmet need. Rapidly controlling EMD to prevent end-organ damage is a priority. Retrospectively, we reviewed our database for patients with EMD that received treatment with bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide (VDPACE) plus an immune modulator (IMiD) regimen. We identified 21 patients with a median age of 61 years. Ten patients received a VDPACE based regimen as a bridge to autologus stem cell transplant (ASCT). After a median follow-up of 51.4 months, the median overall survival (OS) and progression-free survival were 14.9 months (95% CI: 7.8-NA) and 5.5 months (95% CI: 3.9-NA), respectively. The overall response rate was 76%, with a manageable safety profile. Interestingly, these results were similar regardless of the presence of high-risk cytogenetics. The safety profile was acceptable. In conclusion, a salvage VDPACE-based regimen plus an IMiD remains an effective and safe bridging therapy to future ASCT and immunotherapy in relapsed/refractory multiple myeloma patients with EMD.
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Affiliation(s)
- Al‐Ola Abdallah
- Division of Hematologic Malignancies & Cellular TherapeuticsUniversity of Kansas Medical CenterWestwoodKansasUSA
| | | | - Nausheen Ahmed
- Division of Hematologic Malignancies & Cellular TherapeuticsUniversity of Kansas Medical CenterWestwoodKansasUSA
| | - Meera Mohan
- Division of Hematology/OncologyMedical College of WisconsinMilwaukeeWisconsinUSA
| | - Wei Cui
- Division of Pathology & Laboratory MedicineUniversity of Kansas Medical CenterKansas CityKansasUSA
| | - Leyla Shune
- Division of Hematologic Malignancies & Cellular TherapeuticsUniversity of Kansas Medical CenterWestwoodKansasUSA
| | | | - Joseph McGuirk
- Division of Hematologic Malignancies & Cellular TherapeuticsUniversity of Kansas Medical CenterWestwoodKansasUSA
| | - Siddhartha Ganguly
- Division of Hematologic Malignancies & Cellular TherapeuticsUniversity of Kansas Medical CenterWestwoodKansasUSA
| | - Shebli Atrash
- Levine Cancer InstituteCarolinas Healthcare SystemCharlotteNorth CarolinaUSA
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47
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Gaube A, Nica SG, Dobrea C, Neicu SA, Moldoveanu VG, Serbanescu M, Calangiu FS. Radiation response of soft-tissue extramedullary plasmacytoma in multiple myeloma-A case report. Clin Case Rep 2021; 9:e05084. [PMID: 34804534 PMCID: PMC8587684 DOI: 10.1002/ccr3.5084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/12/2021] [Accepted: 10/14/2021] [Indexed: 11/26/2022] Open
Abstract
We report the case of a 79-year-old female patient previously treated for multiple myeloma that was referred to our hospital due to a growing painless right arm tumor. Imaging and pathology results confirmed the diagnosis of extramedullary plasmacytoma. The patient underwent external beam radiotherapy with complete clinical response at follow-up.
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Affiliation(s)
- Alexandra Gaube
- National Institute of Infectious Diseases “Prof. Dr. Matei Bals”BucharestRomania
| | | | - Camelia Dobrea
- Fundeni Clinical InstituteBucharestRomania
- “Carol Davila” University of Medicine and PharmacyBucharestRomania
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48
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Ramos AL, Trindade M, Santos Pinto A, Brandão JR, Pedrosa C, Pinto A. Pleural effusion and multiple myeloma - more than meets the eye: A case report. Mol Clin Oncol 2021; 15:238. [PMID: 34650805 PMCID: PMC8506683 DOI: 10.3892/mco.2021.2401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 08/13/2021] [Indexed: 11/05/2022] Open
Abstract
Multiple myeloma (MM) accounts for 1% of all cancers. It consists of malignant proliferation of plasma cells, which is often associated with hypersecretion of a monoclonal protein. Pleural effusion (PE) in MM is not an uncommon finding, comprising about 6-14% of patients with MM. The most common causes of MM-associated PE are congestive heart failure, renal failure, parapneumonic effusion and amyloidosis. In <1% of cases, the effusion is a direct result of MM, designated as myelomatous PE (MPE). MPE is usually a diagnosis of exclusion and carries a poor prognosis. Therefore, efforts should be made to optimally detect MPE. The present report describes an MPE associated with IgG/λ MM presenting as a septic shock and renal failure in which a rare diagnosis was made after excluding all other possible etiologies in a complex intensive care patient.
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Affiliation(s)
- Ana Luísa Ramos
- Pulmonology Department, Egas Moniz Hospital, 1349-019 Lisbon, Portugal
| | - Miguel Trindade
- Medicine Department, Fernando Fonseca Hospital, 2720-276 Amadora, Portugal
| | - André Santos Pinto
- Medicine Department, West Hospital Center-Torres Vedras, 2560-324 Torres Vedras, Portugal
| | - José Ricardo Brandão
- Department of Pathological Anatomy, University Hospital Center of Porto, 4099-901 Porto, Portugal
| | - Cláudia Pedrosa
- Department of Clinical Hematology, University Hospital Center of Porto, 4099-901 Porto, Portugal
| | - Alexandre Pinto
- Department of Intensive Care, University Hospital Center of Porto, 4099-901 Porto, Portugal
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49
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Bansal R, Rakshit S, Kumar S. Extramedullary disease in multiple myeloma. Blood Cancer J 2021; 11:161. [PMID: 34588423 PMCID: PMC8481260 DOI: 10.1038/s41408-021-00527-y] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 06/07/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
When clonal plasma cells grow at anatomic sites distant from the bone marrow or grows contiguous from osseous lesions that break through the cortical bone, it is referred to as extramedullary multiple myeloma (EMD). EMD remains challenging from a therapeutic and biological perspective. The pathogenetic mechanisms are not completely understood and it is generally associated with high-risk cytogenetics which portends poor outcomes. There is a rising incidence of EMD in the era of novel agents, likely a reflection of longer OS, with no standard treatment approach. Patients benefit from aggressive chemotherapy-based approaches, but the OS and prognosis remains poor. RT has been used for palliative care. There is a need for large prospective trials for development of treatment approaches for treatment of EMD.
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Affiliation(s)
- Radhika Bansal
- Division of Hematology, Mayo Clinic, Rochester, MN, USA, 55905
| | - Sagar Rakshit
- Division of Hematology, Mayo Clinic, Rochester, MN, USA, 55905
| | - Shaji Kumar
- Division of Hematology, Mayo Clinic, Rochester, MN, USA, 55905.
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50
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Deng H, Liu M, Yuan T, Zhang H, Cui R, Li J, Yuan J, Wang X, Wang Y, Deng Q. Efficacy of Humanized Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With and Without Extramedullary Disease. Front Immunol 2021; 12:720571. [PMID: 34421924 PMCID: PMC8374046 DOI: 10.3389/fimmu.2021.720571] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/14/2021] [Indexed: 01/22/2023] Open
Abstract
In recent years, many new treatments for relapsed/refractory (R/R) multiple myeloma (MM) have improved patient prognosis, but the prognosis of patients with extramedullary MM is still particularly poor. Therefore, more efficacious therapies and novel strategies are urgently needed for these patients. The aim of this study was to observe and compare the efficacy and safety of humanized anti-B cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cell therapy in R/R MM patients with and without extramedullary disease. Seven R/R MM patients with extramedullary disease and 13 without extramedullary disease received humanized anti-BCMA CAR T cell therapy. The overall response rate was not different between patients with and without extramedullary disease. There was no difference in the progression-free survival (PFS) or overall survival (OS) rates between the two groups at 180 days, but the PFS and OS rates in patients with extramedullary disease were lower at 360 days than those in patients without extramedullary disease. Although some patients with extramedullary disease experienced further disease progression, their M protein level did not increase. We did not see this change trend of M protein in patients without extramedullary disease. However, this was not observed in patients without extramedullary disease. Among patients who responded to CAR T cell therapy, the grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS) were much higher among patients with extramedullary disease. In summary, R/R MM patients with extramedullary disease could benefit from humanized anti-BCMA CAR T cell therapy in the short term, although the CRS and ICANS grades were much higher in patients with extramedullary disease. Therefore, anti-BCMA CAR T cell therapy allows for a remission time for R/R MM patients with extramedullary disease, which could be maintained by bridging hematopoietic stem cell transplantation, radiotherapy, and other therapies. Clinical Trial Registration http://www.chictr.org.cn/index.aspx, identifiers ChiCTR1800017051 and ChiCTR2000033925.
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Affiliation(s)
- Haobin Deng
- First Central Clinical College, Tianjin Medical University, Tianjin, China
| | - Meijing Liu
- First Central Clinical College, Tianjin Medical University, Tianjin, China
| | - Ting Yuan
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Huan Zhang
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Rui Cui
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Jingyi Li
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Jijun Yuan
- Shanghai Genbase Biotechnology Co., Ltd., Shanghai, China
| | - Xiaofang Wang
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yafei Wang
- Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Qi Deng
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
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