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Keski H, Merdan S, Zemheri IE. Evaluation of CD56 and CD117 Double-Positivity as a Predictor of Poor Prognosis in Multiple Myeloma Patients: A Retrospective Analysis. Turk J Haematol 2024; 41:236-245. [PMID: 39377029 PMCID: PMC11628754 DOI: 10.4274/tjh.galenos.2024.2024.0149] [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: 04/26/2024] [Accepted: 10/08/2024] [Indexed: 10/09/2024] Open
Abstract
Objective Despite advancements in treatment, multiple myeloma (MM) remains a challenging hematologic malignancy. It is crucial to stratify risk and perform prognostic assessment with various markers, including the expression of cluster of differentiation 56 (CD56) and cluster of differentiation 117 (CD117). However, the relationship of these markers with MM-related survival remains unclear. In this context, the objective of this study was to investigate the prognostic implications of CD56 and CD117 expression and associated clinical features in MM patients. Materials and Methods The population of this retrospective single-center study consisted of adult MM patients whose CD56 and CD117 expression levels were analyzed. Patients were divided into four groups according to their immunophenotypes: CD56+CD117-, CD56-CD117+, CD56+CD117+, and CD56-CD117-. These groups were compared in terms of demographic and clinical characteristics, response to treatment, and survival outcomes. Results Of the 168 MM patients included in the study, CD56 positivity, CD117 positivity, CD56 and CD117 double positivity, and CD56 and CD117 double negativity were observed in 57.1%, 38.1%, 21.4%, and 26.2%, respectively. Patients with double positivity had significantly higher cytogenetic risk and significantly lower overall response rate (ORR) compared to other patients (p<0.001 for both). ORR and overall survival (OS) were significantly lower in CD56-positive patients than in CD56-negative patients (p=0.017 and p=0.004, respectively). Mortality rates were significantly higher in CD56-positive and CD117-positive patients than in double-negative patients (p<0.001 and p=0.002, respectively). Double-negative patients had significantly lower ORR and OS and higher mortality than others (p=0.001, p=0.002, and p<0.001, respectively). High cytogenetic risk was found to be an independent predictor of shorter OS (p>0.001). Conclusion This study’s findings revealed that MM patients with CD56 and CD117 double positivity had poorer prognosis, lower ORR, shorter OS, and higher mortality.
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Affiliation(s)
- Hakan Keski
- University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Hematology, İstanbul, Türkiye
| | - Selim Merdan
- University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Microbiology, İstanbul, Türkiye
| | - Itır Ebru Zemheri
- University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Pathology, İstanbul, Türkiye
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2
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Karadag FK, Aysin M, Soyer N, Güneş A, Bozer D, Demir D, Arslan A, Sahin F, Töbü M, Saydam G, Vural F. Does immunohistochemical staining predict mobilization success in multiple myeloma patients? Transfus Apher Sci 2024; 63:104004. [PMID: 39288703 DOI: 10.1016/j.transci.2024.104004] [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: 07/31/2024] [Revised: 09/11/2024] [Accepted: 09/13/2024] [Indexed: 09/19/2024]
Abstract
BACKGROUND So many risk factors for mobilization failure have been described so far. We aimed to identify the risk factors and search the possible effects of bone marrow fibrosis (BMF), CD56, c-myc, and cyclinD1 expression on mobilization. METHODS We evaluated 189 patients with MM who were admitted for stem cell mobilization before autologous stem cell transplantation (ASCT) between 2015 and June 2021. Clinical, laboratory, treatment features, and survival outcomes were compared in patients who were successfully mobilized and who were not. RESULTS Mobilization failure rate was 11.1 % (21) in our study group. Male gender, mobilization with only G-CSF, history of previous ASCT, lenalidomide exposure, and 2 lines of chemotherapy before stem cell mobilization were observed more commonly in mobilization failure group. There is no relationship between mobilization failure and BMF, CD56, c-myc, and cyclin D1 expression status in patients who received either only G-CSF or G-CSF+ chemotherapy for mobilization. Overall survival (OS) was not different in groups of patients who were successfully mobilized and who were not. Neutrophil engraftment was faster in patients who were transfused > 5 × 106/kg stem cells (p = 0.015). ECOG performance status (p = 0.004), c-myc expression (p = 0.005), lenalidomide therapy before mobilization (p = 0.032), and mobilization with G-CSF+chemotherapy was found to be predictive factors for OS. CONCLUSION Even though we could not find any predictive value of CD56, c-myc, and cyclin D1 expression on mobilization, c-myc was found to be associated with low OS. Further studies with large and homogenous study population would be more informative.
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Affiliation(s)
| | - Murat Aysin
- Balıkesir University, Faculty of Medicine, Department of Public Health, Balıkesir, Turkey
| | - Nur Soyer
- Ege University Medical School, Department of Hematology, Izmir, Turkey
| | - Ajda Güneş
- Ege University Medical School, Department of Hematology, Izmir, Turkey
| | - Denis Bozer
- Ege University Medical School, Department of Hematology, Izmir, Turkey
| | - Derya Demir
- Ege University Medical School, Department of Pathology, Izmir, Turkey.
| | - Aysenur Arslan
- University of Ulm, Institute of Transfusion Medicine, Ulm, Germany
| | - Fahri Sahin
- Ege University Medical School, Department of Hematology, Izmir, Turkey
| | - Mahmut Töbü
- Ege University Medical School, Department of Hematology, Izmir, Turkey.
| | - Guray Saydam
- Ege University Medical School, Department of Hematology, Izmir, Turkey
| | - Filiz Vural
- Ege University Medical School, Department of Hematology, Izmir, Turkey
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Gupta R, Jevremovic D, Mathew SJ, Kumar S. Multiparametric Flow Cytometry in the Evaluation of Plasma Cell Proliferative Disorders: Current Paradigms for Clinical Practice. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2024; 24:e88-e95. [PMID: 38142203 DOI: 10.1016/j.clml.2023.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 12/25/2023]
Abstract
Diagnosis of plasma cell proliferative disorders (PCPDs) is primarily based on the demonstration of monoclonal protein (M-Protein) in blood and/ or urine which often precedes clinical manifestations of the disease. The basic pathophysiology behind the M-protein presence is the proliferation of clonal plasma cells (PCs) in bone marrow or extramedullary sites and is assessed using cytomorphology and immunophenotyping. The role of multiparametric flow cytometry (MFC) for PC identification is technically the most valuable tool in this context as it characterizes as well as quantifies the clonal PCs based on differential expression of various immunophenotypic (IPT) markers. From a diagnostic perspective, MFC is critical in the definite identification of the clonal PCs and delineates benign and borderline entities at one end of the spectrum (MGUS, SMM) with lower clonal PC% and, malignant diseases at the other end (MM and PCL) with higher clonal PC fraction. The role of MFC in assessment of measurable residual disease (MRD) and monitoring of progression in MM and various PCPDs has been validated in multiple clinical studies and is probably one of the most promising tools for predicting treatment outcomes. Furthermore, MFC also plays a crucial role in disease prognostication based on specific IPT profiles. An additional role of MFC in the current clinical scenario is the evaluation of tumor microenvironment based on immune cell repertoire, which is reflecting encouraging results across. Thus, in the current review we concisely describe the role of MFC as a reliable and essential modality in PCPDs, from diagnosis to prediction of treatment outcome and disease monitoring.
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Affiliation(s)
- Ritu Gupta
- Department of Laboratory Oncology, Dr. BRAIRCH, AIIMS, New Delhi, India; Department of Hematology, Mayo Clinic, Rochester, MN.
| | - Dragan Jevremovic
- Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN
| | | | - Shaji Kumar
- Department of Hematology, Mayo Clinic, Rochester, MN
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Notarfranchi L, Segreto R, Vescovini R, Dalla Palma AB, Marchica V, Burroughs-Garcia J, Toscani D, Todaro G, Raimondi V, Iannozzi NT, Bonomini S, Sammarelli G, Craviotto L, Pedrazzoni M, Storti P, Giuliani N. The impact of CD56 expression in smoldering myeloma patients on early progression. Hematol Oncol 2023; 41:587-589. [PMID: 36441875 DOI: 10.1002/hon.3104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Laura Notarfranchi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Hematology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Roberta Segreto
- Hematology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Rosanna Vescovini
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | | | | | | | - Denise Toscani
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Giannalisa Todaro
- Hematology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Vincenzo Raimondi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | | | - Sabrina Bonomini
- Hematology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | | | - Luisa Craviotto
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Hematology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Mario Pedrazzoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Paola Storti
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Nicola Giuliani
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Hematology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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5
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Asherie N, Kfir-Erenfeld S, Avni B, Assayag M, Dubnikov T, Zalcman N, Lebel E, Zimran E, Shaulov A, Pick M, Cohen Y, Avivi I, Cohen C, Gatt ME, Grisariu S, Stepensky P. Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Haematologica 2023; 108:1827-1839. [PMID: 36200421 PMCID: PMC10316256 DOI: 10.3324/haematol.2022.281628] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 09/23/2022] [Indexed: 11/09/2022] Open
Abstract
Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM). HBI0101, a novel second generation optimized anti- BCMA CAR T-cell therapy, was developed in an academic setting. We conducted a phase I dose-escalation study of HBI0101 (cohort 1: 150x106 CAR T cells, n=6; cohort 2: 450x106 CAR T cells, n=7; cohort 3: 800x106 CAR T cells, n=7) in 20 heavily pre-treated R/R MM patients. Grade 1-2 cytokine release syndrome (CRS) was reported in 18 patients (90%). Neither grade 3-4 CRS nor neurotoxicity of any grade were observed. No dose-limiting toxicities were observed in any cohort. The overall response rate (ORR), (stringent) complete response (CR/sCR), and very good partial response rates were 75%, 50%, and 25%, respectively. Response rates were dose-dependent with 85% ORR, 71% CR, and 57% minimal residual disease negativity in the high-dose cohort 3. Across all cohorts, the median overall survival (OS) was 308 days (range 25-466+), with an estimated OS of 55% as of June 27th (data cut-off). The median progression-free survival was 160 days, with 6 subjects remaining progression free at the time of data cut-off. Our findings demonstrate the manageable safety profile and efficacy of HBI0101. These encouraging data support the decentralization of CAR T production in an academic setting, ensuring sufficient CAR T supply to satisfy the increasing local demand. Clinicaltrials.gov NCT04720313.
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Affiliation(s)
- Nathalie Asherie
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem.
| | - Shlomit Kfir-Erenfeld
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Batia Avni
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Miri Assayag
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Tatyana Dubnikov
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Nomi Zalcman
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Eyal Lebel
- Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Eran Zimran
- Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Adir Shaulov
- Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Marjorie Pick
- Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Yael Cohen
- Department of Hematology, Aviv Medical Center, Sackler faculty of medicine, Aviv University
| | - Irit Avivi
- Department of Hematology, Aviv Medical Center, Sackler faculty of medicine, Aviv University
| | - Cyrille Cohen
- Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900-02, Israel
| | - Moshe E Gatt
- Department of Hematology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Sigal Grisariu
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem
| | - Polina Stepensky
- Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem.
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Mengich I, Rajput S, Malkit R, Moloo Z, Kagotho E, Lalani EN, Mwirigi A. Immunophenotypic expression profile of multiple myeloma cases at a tertiary hospital in Nairobi Kenya. Front Med (Lausanne) 2023; 10:1177775. [PMID: 37250623 PMCID: PMC10213391 DOI: 10.3389/fmed.2023.1177775] [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: 03/02/2023] [Accepted: 04/17/2023] [Indexed: 05/31/2023] Open
Abstract
Introduction Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10-15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously. Methods A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher's exact test was used to determine the association between the immunophenotypic markers and categorical variables. Results Of the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki-67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden. Conclusion Cyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies.
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Affiliation(s)
- Isabella Mengich
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | - Sheerien Rajput
- Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan
- Centre for Regenerative Medicine and Stem Cell Research, Aga Khan University, Karachi, Pakistan
| | - Riyat Malkit
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | - Zahir Moloo
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | - Elizabeth Kagotho
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | - El-Nasir Lalani
- Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan
- Centre for Regenerative Medicine and Stem Cell Research, Aga Khan University, Karachi, Pakistan
| | - Anne Mwirigi
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
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7
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Geng C, Zhou H, Wang H, Li Y, Leng Y, Zhang Z, Jian Y, Yang G, Chen W. Newly diagnosed multiple myeloma patients with CD56 expression benefit more from autologous stem cell transplantation. BMC Cancer 2022; 22:1349. [PMID: 36564753 PMCID: PMC9783713 DOI: 10.1186/s12885-022-10382-0] [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: 09/18/2022] [Accepted: 11/29/2022] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Several studies showed that lack of CD56 expression was a poor prognostic factor for patients with newly diagnosed multiple myeloma (NDMM). However, other studies were not able to confirm the prognostic value of CD56 in NDMM. This study aimed to evaluate the prognostic value of CD56 expression for patients with NDMM who received autologous stem cell transplantation (ASCT). METHODS We retrospectively analyzed 370 patients with NDMM under 66 years old and the propensity score matching technique was used to reduce the bias between two groups. RESULTS CD56 expression was observed in 250 (67.6%) patients, and only half of transplant-eligible patients received ASCT for financial and adverse effects concerns after induction therapy. 54.8% (137/250) CD56 positive patients received ASCT; and 47.5% (57/120) CD56 negative patients received ASCT. Univariate and multivariate analyses showed that ASCT was correlated with longer overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) for CD56 positive patients. However, ASCT had no impact on OS and PFS in univariate and multivariate analysis (p > 0.05). In the propensity score matching analysis, 186 CD56 positive patients were identified, 93 patients had received ASCT and 93 patients had no ASCT. Among 120 CD56 negative patients, 80 patients, 40 in each group, were identified. Among 186 matched CD56 positive patients, patients with ASCT had longer OS (87.6 vs.56.1 months, p = 0.049) and PFS (36.7 vs.30.9 months, p = 0.040). However, ASCT had no impact on OS and PFS for matched CD56 negative patients (p > 0.05). CONCLUSIONS These results demonstrated that ASCT may improve OS and PFS of CD56 positive patients and had no impact on survival of CD56 negative patients.
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Affiliation(s)
- Chuanying Geng
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Huixing Zhou
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Huijuan Wang
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Yanchen Li
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Yun Leng
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Zhiyao Zhang
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Yuan Jian
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Guangzhong Yang
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
| | - Wenming Chen
- grid.24696.3f0000 0004 0369 153XDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 China
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Qu C, Zhang H, Cao H, Tang L, Mo H, Liu F, Zhang L, Yi Z, Long L, Yan L, Wang Z, Zhang N, Luo P, Zhang J, Liu Z, Ye W, Liu Z, Cheng Q. Tumor buster - where will the CAR-T cell therapy 'missile' go? Mol Cancer 2022; 21:201. [PMID: 36261831 PMCID: PMC9580202 DOI: 10.1186/s12943-022-01669-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/26/2022] [Indexed: 11/10/2022] Open
Abstract
Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.
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Affiliation(s)
- Chunrun Qu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,XiangYa School of Medicine, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Hao Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.,Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Hui Cao
- Department of Psychiatry, The Second People's Hospital of Hunan Province, The Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.,The School of Clinical Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Lanhua Tang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Haoyang Mo
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,XiangYa School of Medicine, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Fangkun Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Liyang Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhenjie Yi
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,XiangYa School of Medicine, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lifu Long
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,XiangYa School of Medicine, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Luzhe Yan
- XiangYa School of Medicine, Central South University, Changsha, Hunan, China
| | - Zeyu Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Nan Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.,One-third Lab, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China
| | - Peng Luo
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jian Zhang
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou, Zhengzhou, Henan, China
| | - Weijie Ye
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhixiong Liu
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
| | - Quan Cheng
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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9
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Li L, Li X, Shang A, Zhao Y, Jin L, Zhao M, Shen W. Prognostic significance of CD56 antigen in newly diagnosed multiple myeloma: A real-world retrospective study. Medicine (Baltimore) 2022; 101:e30988. [PMID: 36221376 PMCID: PMC9542762 DOI: 10.1097/md.0000000000030988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The prognostic value of plasma cell CD56 expression of patients with multiple myeloma (MM) has been reported in many studies, but the results are controversial. This study aimed to examine the prognostic significance of CD56 in MM patients. Eighty seven patients with newly diagnosed MM were enrolled in this study, and their clinical characteristics, immunophenotypes, and cytogenetics were retrospectively analyzed to explore the prognostic significance of CD56 expression. Multiparameter flow cytometry was used to detect MM in bone marrow samples from all patients. Patients were divided into 2 groups based on whether they expressed CD56: CD56 + group and CD56 - group. After 4 cycles of chemotherapy, the overall response rate of the CD56 - patients was lower than that of the CD56 + patients (60.0% vs 81.1%, P = .036). Survival analysis showed that the median progression-free survival (PFS) was 10 months for the CD56 - group and 27 months for the CD56 + group (P = .007). The median overall survival (OS) of patients for the CD56 - group was 25 months versus not reached in the CD56 + group (P = .010). In addition, among the high-risk patients detected by fluorescence in situ hybridization (FISH), the median PFS was 4 months for the CD56 - group and 16 months for the CD56 + group (P = .012). The median OS of the CD56 + group and CD56 - group was 36 months and 15 months, respectively, with statistically significant differences (P = .017). Our study confirmed that CD56 - patients with MM had a worse prognosis than that of CD56 + patients with MM. Among the patients with ≥ 2 high-risk cytogenetics, the existence of the CD56 negativity can further identify MM patients with poor PFS and OS.
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Affiliation(s)
- Liping Li
- Department of Oncology and Hematology, The Second Hospital of Jilin University, Nanguan District, Changchun City, Jilin, China
| | - Xiaofeng Li
- Department of Oncology and Hematology, The Second Hospital of Jilin University, Nanguan District, Changchun City, Jilin, China
| | - An Shang
- Department of Oncology and Hematology, The Second Hospital of Jilin University, Nanguan District, Changchun City, Jilin, China
| | - Yan Zhao
- Department of Oncology and Hematology, The Second Hospital of Jilin University, Nanguan District, Changchun City, Jilin, China
| | - Lifang Jin
- Department of Oncology and Hematology, The Second Hospital of Jilin University, Nanguan District, Changchun City, Jilin, China
| | - Meng Zhao
- Department of Oncology and Hematology, The Second Hospital of Jilin University, Nanguan District, Changchun City, Jilin, China
| | - Weizhang Shen
- Department of Oncology and Hematology, The Second Hospital of Jilin University, Nanguan District, Changchun City, Jilin, China
- *Correspondence: Weizhang Shen, Department of Oncology and Hematology, The Second Hospital of Jilin University, No 218, Lane Ziqiang, Nanguan District, Changchun City, Jilin Province, 130041, China (e-mail: )
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10
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Cottini F, Rodriguez J, Hughes T, Sharma N, Guo L, Lozanski G, Liu B, Cocucci E, Yang Y, Benson D. Redefining CD56 as a biomarker and therapeutic target in Multiple Myeloma. Mol Cancer Res 2022; 20:1083-1095. [PMID: 35380709 DOI: 10.1158/1541-7786.mcr-21-0828] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 02/11/2022] [Accepted: 03/29/2022] [Indexed: 11/16/2022]
Abstract
Multiple myeloma (MM) cells aberrantly express surface antigens compared to normal plasma cells. Among others, CD56 is present at variable levels in approximately 70% of MM patients; however very little is known about CD56 role in MM. We demonstrated that MM patients with more than 10 percent of CD56-expressing clonal MM cells have inferior clinical outcomes. By gain-of and loss-of function models, we revealed that CD56 promotes MM cell growth, survival, and adhesion to stromal cells. These protumoral effects are induced by the activation of the RSK2/CREB1 signaling pathway, with increased mRNA and protein levels of the anti-apoptotic genes BCL2 and MCL1. Consequently, the genomic and pharmacological inhibition of RSK2 or CREB1 specifically induced MM cell death in CD56-expressing MM cells. Finally, we observed that CD56 signaling decreases CRBN expression, reducing responses to lenalidomide. RSK2 or CREB1 inhibition increased CRBN levels and were synergic with lenalidomide in inducing cell death, especially in CD56-expressing MM cells. In conclusion, our findings demonstrate that CD56 promotes MM cell growth, and pave the way to novel therapies based on targeting CD56, along with the use of CD56 as a predictive biomarker for MM therapies. Implications: Multiple myeloma (MM) is an incurable, genetically heterogeneous disease, without available tailored therapeutic approaches. CD56 signaling promotes MM growth and adhesion, by activating CREB1 target genes, MCL1 and BCL2. Inhibition of CREB1 alone or in combination with lenalidomide is an unexplored synthetic lethal approach in CD56-expressing MM patients.
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Affiliation(s)
- Francesca Cottini
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Jose Rodriguez
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio
| | - Tiffany Hughes
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio
| | - Nidhi Sharma
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio
| | - Ling Guo
- Department of Pathology, OhioHealth, Columbus, Ohio
| | - Gerard Lozanski
- Department of Pathology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Bei Liu
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Emanuele Cocucci
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
- The Ohio State University, College of Pharmacy, Columbus, Ohio
| | - Yiping Yang
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Don Benson
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
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11
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Lebel E, Nachmias B, Pick M, Gross Even-Zohar N, Gatt ME. Understanding the Bioactivity and Prognostic Implication of Commonly Used Surface Antigens in Multiple Myeloma. J Clin Med 2022; 11:jcm11071809. [PMID: 35407416 PMCID: PMC9000075 DOI: 10.3390/jcm11071809] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/19/2022] [Accepted: 03/23/2022] [Indexed: 02/06/2023] Open
Abstract
Multiple myeloma (MM) progression is dependent on its interaction with the bone marrow microenvironment and the immune system and is mediated by key surface antigens. Some antigens promote adhesion to the bone marrow matrix and stromal cells, while others are involved in intercellular interactions that result in differentiation of B-cells to plasma cells (PC). These interactions are also involved in malignant transformation of the normal PC to MM PC as well as disease progression. Here, we review selected surface antigens that are commonly used in the flow cytometry analysis of MM for identification of plasma cells (PC) and the discrimination between normal and malignant PC as well as prognostication. These include the markers: CD38, CD138, CD45, CD19, CD117, CD56, CD81, CD27, and CD28. Furthermore, we will discuss the novel marker CD24 and its involvement in MM. The bioactivity of each antigen is reviewed, as well as its expression on normal vs. malignant PC, prognostic implications, and therapeutic utility. Understanding the role of these specific surface antigens, as well as complex co-expressions of combinations of antigens, may allow for a more personalized prognostic monitoring and treatment of MM patients.
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12
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Zhang L, Huang Y, Lin Y, Zhang A, Zou R, Xu H, Wang S. Prognostic significance of CD56 expression in patients with multiple myeloma: a meta-analysis. Hematology 2022; 27:122-131. [PMID: 35068378 DOI: 10.1080/16078454.2021.2019365] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Affiliation(s)
- Lijuan Zhang
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Yun Huang
- Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Yun Lin
- Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Aili Zhang
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Rong Zou
- Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Huiying Xu
- Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Sili Wang
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
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13
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Zhang DY, Huang GR, Ku JW, Zhao XK, Song X, Xu RH, Han WL, Zhou FY, Wang R, Wei MX, Wang LD. Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus. World J Clin Cases 2021; 9:9011-9022. [PMID: 34786384 PMCID: PMC8567530 DOI: 10.12998/wjcc.v9.i30.9011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 06/19/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary small cell carcinoma of the esophagus (PSCE) is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma. Due to the limited samples size and the short follow-up time, there are few reports on elucidating the prognosis of PSCE, especially on the establishment and validation of a survival prediction nomogram model covering general information, pathological factors and specific biological proteins of PSCE patients.
AIM To establish an effective nomogram to predict the overall survival (OS) probability for PSCE patients in China.
METHODS The nomogram was based on a retrospective study of 256 PSCE patients. Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE, and establish the model for predicting 1-, 3-, and 5-year OS based on the Akaike information criterion. Discrimination and validation were assessed by the concordance index (C-index) and calibration curve and decision curve analysis (DCA). Histology type, age, tumor invasion depth, lymph node invasion, detectable metastasis, chromogranin A, and neuronal cell adhesion molecule 56 were integrated into the model.
RESULTS The C-index was prognostically superior to the 7th tumor node metastasis (TNM) staging in the primary cohort [0.659 (95%CI: 0.607-0.712) vs 0.591 (95%CI: 0.517-0.666), P = 0.033] and in the validation cohort [0.700 (95%CI: 0.622-0.778) vs 0.605 (95%CI: 0.490-0.721), P = 0.041]. Good calibration curves were observed for the prediction probabilities of 1-, 3-, and 5-year OS in both cohorts. DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging .
CONCLUSION Our nomogram can be used to predict the survival probability of PSCE patients, which can help clinicians to make individualized survival predictions.
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Affiliation(s)
- Dong-Yun Zhang
- Department of Pathology, Nanyang Medical College, Nanyang 473061, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Gai-Rong Huang
- Department of Geriatrics, Henan People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Jian-Wei Ku
- Department of Endoscopy of The Third Affiliated Hospital, Nanyang Medical College, Nanyang 473061, Henan Province, China
| | - Xue-Ke Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Xin Song
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Rui-Hua Xu
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Wen-Li Han
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Fu-You Zhou
- Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
| | - Ran Wang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Meng-Xia Wei
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Li-Dong Wang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
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14
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ElMenshawy N, Farag NA, Atia DM, Abousamra N, Shahin D, Fawzi E, Ghazi H, El-Kott AF, Eissa M. Prognostic Relevance of Concordant Expression CD69 and CD56 in Response to Bortezomib Combination Therapy in Multiple Myeloma Patients. Cancer Invest 2021; 39:777-782. [PMID: 34344244 DOI: 10.1080/07357907.2021.1964521] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Multiple myeloma is an incurable hematological malignancy. Currently, the use of proteasome inhibitors could be superior to chemotherapy-based regimen in the treatment of this disease. However, resistance to bortezomib combination therapy still occurs in some patients. So, this research work aims to assess CD69 and CD56 expression in these cases and their relation to the response to therapy. MATERIALS AND METHODS Immunophenotyping by 4-color multi-parameter flow cytometry was carried out on 98 multiple myeloma cases. Clonal plasma cells were gated by co-expression of CD38 with CD138 with low SSC, negative or dim CD45. RESULTS Double negative CD69 and CD56 (47.9%) multiple myeloma cases were associated with high serum β2 microglobulin, creatinine, calcium and low serum albumin. There was also a significant correlation between the absence of these markers with osteolytic lesions and unfavorable cytogenetic t (4;14) (p < 0.001). Moreover, there was a highly significant correlation between CD69- and CD56- with non-response to bortezomib combination therapy in multiple myeloma patients (p < 0.0001). Regression analysis for the prediction of non- response to treatment in these cases using different prognostic indicators revealed that high serum β2 microglobulin, unfavorable cytogenetic, advanced stage, and low expression of CD69 and CD56 were poor predictors of non-response. CONCLUSION CD69 in association with CD56 could be an independent prognostic factor in multiple myeloma cases. It could be used in the routine laboratory assessment for refining stratification and timely therapeutic decision for highly cost therapy in developing countries.
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Affiliation(s)
- Nadia ElMenshawy
- Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt
| | - Nora A Farag
- Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt
| | - Doaa M Atia
- Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt
| | - Nashwa Abousamra
- Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt
| | - Doaa Shahin
- Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt
| | - Eman Fawzi
- Clinical Pathology Department, Hematology Unit, Mansoura Medical School, Mansoura University, Mansoura, Egypt
| | - Hayam Ghazi
- Department of Medical Oncology, Mansoura Oncology Center, Mansoura University, Mansoura, Egypt
| | - Attalla F El-Kott
- Department of Biology, College of Science, King Khalid University, Saudi Arabia.,Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Mohamed Eissa
- Pathology Department, College of Medicine, King Khalid University, Abha, KSA.,Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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15
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Fliss E, Zaretski A, Cohen Y, Shapira Y, Gur E, Yanko R. Outside the box-Surgery for aggressive plasmacytoma in scar. Clin Case Rep 2021; 9:1325-1329. [PMID: 33768837 PMCID: PMC7981673 DOI: 10.1002/ccr3.3761] [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: 05/31/2020] [Revised: 07/25/2020] [Accepted: 07/28/2020] [Indexed: 11/26/2022] Open
Abstract
This report introduces the concept of large-scale surgery and reconstruction when all other medical means of treatment have failed. In select cases, this may act as a mode of buying time and allowing the patient to receive second- or third-line treatments.
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Affiliation(s)
- Ehud Fliss
- Department of Plastic SurgeryTel Aviv Sourasky Medical CenterTel AvivIsrael
| | - Arik Zaretski
- Department of Plastic SurgeryTel Aviv Sourasky Medical CenterTel AvivIsrael
| | - Yael Cohen
- Division of HematologyTel Aviv Sourasky Medical CenterTel AvivIsrael
| | - Yuval Shapira
- Department of NeurosurgeryTel Aviv Sourasky Medical CenterTel AvivIsrael
| | - Eyal Gur
- Department of Plastic SurgeryTel Aviv Sourasky Medical CenterTel AvivIsrael
| | - Ravit Yanko
- Department of Plastic SurgeryTel Aviv Sourasky Medical CenterTel AvivIsrael
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16
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Ding L, Hu Y, Huang H. Novel progresses of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma. Stem Cell Investig 2021; 8:1. [PMID: 33575314 DOI: 10.21037/sci-2020-029] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 12/11/2020] [Indexed: 12/31/2022]
Abstract
Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, which leads to suppressed hematopoietic and osteolytic diseases. Despite the use of traditional chemotherapy, hematopoietic stem cell transplantation (HSCT) and targeted drugs, MM still cannot be completely cured. In recent years, chimeric antigen receptor (CAR) T cells have revolutionized immunotherapy and cancer treatment. The great success of CAR-T cells in leukemia and lymphoma has promoted its development in MM. The primary requisite for developing clinically effective CAR-T cells suitable for MM is to identify the appropriate targets. In early clinical trials, CAR-T cells targeting B-cell maturation antigen (BCMA) have shown significant anti-MM activity. Currently popular targets in clinical research and preclinical research include CD138, CD38, CS1, CD19, κ light chain, CD56, CD44v6, Lewis Y, NY-ESO-1, CD229, etc. Common toxicities such as cytokine release syndrome (CRS) and neurotoxicity also occur but controllable. MM cells are mainly localized in bone marrow, therefore, the bone marrow microenvironment has a significant effect on the therapeutic effect of CAR-T cells. Targeting both MM cells and the bone marrow microenvironment is currently the most promising treatment. In this review, we provide a comprehensive overview of CAR-T cell therapy in MM, as well as outline potential targets and methods that can overcome local immunosuppression and improve the efficacy of CAR-T cells.
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Affiliation(s)
- Lijuan Ding
- Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yongxian Hu
- Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Institute of Hematology, Zhejiang University, Hangzhou, China.,Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
| | - He Huang
- Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Institute of Hematology, Zhejiang University, Hangzhou, China.,Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China
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17
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Göçer M, Kurtoğlu E. Is absence of CD56 a predictive factor for peripheral blood stem cell mobilization failure in patients with multiple myeloma? J Clin Apher 2020; 36:332-339. [PMID: 33333593 DOI: 10.1002/jca.21864] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 10/22/2020] [Accepted: 12/06/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND CD56 is believed to play a major role in MM pathogenesis with a 70% to 80% expression rate in malignant plasma cells at the time of diagnosis. Our objective in this study was to investigate the relationship between the characteristics of CD56 expression in bone marrow aspiration material at the time of diagnosis and the success of stem cell mobilization in patients diagnosed with MM. METHODS This monocenter study included 94 patients who were diagnosed with MM and had a stem cell mobilization procedure for autologous hematopoietic stem cell transplantation. The primary endpoint of the study was to compare the mobilization success between the groups with and without CD56 expression. The secondary endpoint was to identify other factors affecting mobilization failure outside CD56. RESULTS At the time of diagnosis, 49 (52.1%) patients had CD56 expression and 45 (47.9%) did not. Mobilization failed in 11 (11.7%) patients. Age, gender, ISS stage and the number of premobilization treatment regimens were not found predictive of mobilization failure. CD56 negativity was 42.2% in the group that had mobilization success and 90.9% in the group that had mobilization failure (P = .001). CONCLUSIONS The fact that CD56 residing on the membrane enables interaction between bone marrow cells and ECM and functions as a signal molecule increases sensitivity to the chemotherapy and G-CSF that are used for mobilization. We found that absence of CD56 can be used as a predictive factor for mobilization failure at the time of diagnosis.
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Affiliation(s)
- Mesut Göçer
- Department of Internal Medicine, Division of Hematology, Antalya Training and Research Hospital, Antalya, Turkey
| | - Erdal Kurtoğlu
- Department of Internal Medicine, Division of Hematology, Antalya Training and Research Hospital, Antalya, Turkey
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18
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The clinical significance of CD49e and CD56 for multiple myeloma in the novel agents era. Med Oncol 2020; 37:103. [PMID: 33068194 DOI: 10.1007/s12032-020-01423-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 09/26/2020] [Indexed: 10/23/2022]
Abstract
Multiple myeloma (MM) is a hematological malignancy characterized by the proliferation of abnormal plasma cells in bone marrow. Flow cytometry distinguishes between normal and abnormal plasma cells by evaluating cluster of differentiation (CD) 56 and CD19 expression patterns. Moreover, immunophenotyping of mature plasma cell 1 (MPC-1) and very late antigen-5 (CD49e) identifies the maturity of MM as mature (MPC-1+, CD49e+), intermediate (MPC-1+, CD49e-), or immature (MPC-1-, CD49e-). We retrospectively examined the effects of surface marker expression and maturity subtype on overall survival (OS) and time to next treatment (TNT) among 55 patients (25 males, 30 females) with symptomatic MM. All patients were treated with regimens containing bortezomib (BOR) (n = 39) or lenalidomide (LEN) (n = 16) as the initial treatment. Median age at diagnosis was 72 years (range: 36-88). The lack of CD56, an aberrant marker, was associated with significantly worse prognosis compared with CD56+ MM (median OS: 24 vs. 60 months, respectively; p = 0.0050). In CD49e+ MM, defined as mature type, no significant difference was seen in TNT of the initial treatment, regardless of whether it was a BOR-based regimen or LEN + dexamethasone (Ld) therapy. On the other hand, in CD49e- MM, defined as immature/intermediate type, TNT of Ld therapy was significantly longer than that of BOR-based regimens (median TNT: undefined vs. 12 months, respectively; p = 0.0043). These results suggest that Ld therapy is more effective than BOR-based therapy for CD49e- MM and thus may aid regimen-related decisions in the novel agents era.
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19
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Inamdar AA, Loo A, Mikhail N, Lee P. Secondary Plasma Cell Leukemia in a Recurrent Multiple Myeloma: Rare Case Scenario. Cureus 2020; 12:e8456. [PMID: 32642366 PMCID: PMC7336714 DOI: 10.7759/cureus.8456] [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] [Indexed: 11/05/2022] Open
Abstract
Plasma cell leukemia (PCL) is an aggressive hematological condition characterized by the presence of plasma cells in the peripheral smear. It presents as de novo or may arise from multiple myeloma (MM), and hence is diagnosed as primary or secondary PCL, respectively. We report a case of 79-year-old patient diagnosed with MM two years prior to the admission to our institution with prior treatment with bortezomib, lenalidomide and dexamethasone (VRD) and daratumumab, pomalidomide and dexamethasone. Morphologic examination and flow cytometry studies performed on the peripheral smear demonstrated 45%-55% small to medium atypical plasma cells showing a kappa restriction and dim CD138 expression on flow cytometry analysis. The patient was started on brentuximab vedotin, etoposide, cytoxan and dexamethasone, which resulted in near complete elimination of the atypical plasma cells from the peripheral smear one week after the completion of two cycles. He received three cycles of brentuximab vedotin with a gradual decrease in serum free light chain. However, he eventually developed lethargy, weakness and seizures. The involvement of the central nervous system (CNS) by MM was confirmed with MRI, flow cytometry and cytology of cerebrospinal fluid. The treatment with whole brain radiation and ibrutinib was initiated. Our case report highlights the rare case of aggressive clinical course of MM leading to the development of plasmacytoma of kidney, secondary PCL and eventually spreading to the CNS.
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Affiliation(s)
| | - Abraham Loo
- Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, USA
| | - Nagy Mikhail
- Pathology, Rutgers Robert Wood Johnson Medical School, New Brunswick, USA
| | - Patrick Lee
- Hematology Oncology, Monmouth Medical Center, Long Branch, USA
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