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1
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Hurtado-Castillo YA, Serrano-Ramírez JA, Juaréz-Sánchez JO, Gaytán-Campos IM. [Therapeutic response and monitoring of antibody-mediated renal graft rejection]. REVISTA MEDICA DEL INSTITUTO MEXICANO DEL SEGURO SOCIAL 2025; 63:e6636. [PMID: 40332680 PMCID: PMC12122064 DOI: 10.5281/zenodo.15178468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 02/28/2025] [Indexed: 05/08/2025]
Abstract
Background Antibody-mediated renal graft rejection is one of the main causes of graft loss. Treatment is based on the removal of circulating antibodies, inhibition of residual antibodies, reduction of their formation, minimization of the alloresponse and terminal complement activation. Objective To assess the therapeutic response in patients who received intravenous immunoglobulin, plasmapheresis, steroid and rituximab as treatment for antibody-mediated renal rejection. Material and methods An applicative, prospective study was carried out in hospitalized patients under the care of a nephrology service with a diagnosis of antibody-mediated rejection of the renal graft according to BANFF. 20 patients were included in 1 year, the biopsy was reviewed in an effort to classify the type of antibody-mediated rejection and the response to treatment was evaluated to demonstrate whether there was stabilization or improvement in renal function at 12 months of follow-up. Results Using the Wilcoxon test, creatinine during the biopsy of the injected and creatinine 12 months after receiving the therapeutic regimen were compared. The Z value was -1.8, with a p = 0.069. Conclusions There was no difference in terms of stabilization or recovery of renal graft function after 12 months of receiving treatment for antibody-mediated rejection based on steroids, plasma exchanges, immunoglobulin and rituximab.
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Affiliation(s)
- Yumar Alfredo Hurtado-Castillo
- Instituto Mexicano del Seguro Social, Centro Médico Nacional del Bajío, Hospital de Especialidades No. 1, Servicio de Nefrología. León, Guanajuato, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - Juana Alejandra Serrano-Ramírez
- Instituto Mexicano del Seguro Social, Centro Médico Nacional del Bajío, Hospital de Especialidades No. 1, Servicio de Nefrología. León, Guanajuato, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - José Oscar Juaréz-Sánchez
- Instituto Mexicano del Seguro Social, Centro Médico Nacional del Bajío, Hospital de Especialidades No. 1, Servicio de Nefrología. León, Guanajuato, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - Itzy Maely Gaytán-Campos
- Instituto Mexicano del Seguro Social, Centro Médico Nacional del Bajío, Hospital de Especialidades No. 1, Servicio de Nefrología. León, Guanajuato, MéxicoInstituto Mexicano del Seguro SocialMéxico
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2
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Zhang YJ, Zhou DJ, Li H, Pan Q, Cheng Y. Prolongated and large dose of r-ATG relieves PD-L1 inhibitor-induced allograft rejection in liver transplant recipient. Hepatobiliary Pancreat Dis Int 2025; 24:221-224. [PMID: 38845248 DOI: 10.1016/j.hbpd.2024.05.005] [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: 11/24/2023] [Accepted: 05/06/2024] [Indexed: 03/22/2025]
Affiliation(s)
- Yi-Jie Zhang
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Dian-Jie Zhou
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Hong Li
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Qi Pan
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Ying Cheng
- Department of Hepatobiliary Surgery and Organ Transplantation, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
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3
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Oteiza Rius I, Morelló Vicente A, Aguado Gil L. [Squamous cell carcinoma in solid organ transplant recipients: Review of the literature]. Med Clin (Barc) 2024; 163:570-576. [PMID: 38981824 DOI: 10.1016/j.medcli.2024.05.005] [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: 01/16/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 07/11/2024]
Abstract
Solid organ transplant recipients (SOTRs) exhibit an elevated incidence and aggressiveness of squamous cell carcinomas (SCCs) due to their immunosuppression. These tumors are associated with a heightened risk of metastasis and increased mortality. Therefore, an appropriate management of these patients is essential to improve their prognosis. Given the scarcity of studies on non-melanoma skin cancers (NMSCs) in SOTRs, this article aims to summarize and analyze the evidence gathered to date regarding therapeutic approaches, personalized monitoring, and prevention strategies for SCCs in these patients. Additionally, recent advancements in understanding SCCs within this patient group are also documented.
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Affiliation(s)
- Inés Oteiza Rius
- Departamento de Dermatología, Clínica Universidad de Navarra, Pamplona, España
| | - Ana Morelló Vicente
- Departamento de Dermatología, Clínica Universidad de Navarra, Pamplona, España.
| | - Leyre Aguado Gil
- Departamento de Dermatología, Clínica Universidad de Navarra, Pamplona, España
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4
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Struckmeier AK, Gosau M, Smeets R. Cutaneous squamous cell carcinoma in solid organ transplant recipients: Current therapeutic and screening strategies. Transplant Rev (Orlando) 2024; 38:100882. [PMID: 39348772 DOI: 10.1016/j.trre.2024.100882] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 09/23/2024] [Accepted: 09/23/2024] [Indexed: 10/02/2024]
Abstract
Solid organ transplant recipients (SOTRs) are particularly prone to developing malignancies, often manifesting multiple tumors and tumors with a heightened susceptibility to metastasis, resulting in much lower survival rates when compared to the general population. Among these, cutaneous squamous cell carcinoma (CSCC) respresent a major challenge in terms of morbidity and mortality following organ transplantation. The management of post-transplant CSCC requires expertise from various disciplines, including dermatology, maxillofacial surgery, transplant medicine, radiation oncology, and medical oncology. Furthermore, the unique behaviors and prevalence of tumors in SOTRs necessitate tailored pathways for screening and treatment, distinct from those designed for immunocompetent patients. Despite the proven efficacy of immune checkpoint inhibitors (ICIs) in several cancers, SOTRs have often been systematically excluded from clinical trials due to concerns about potential allograft rejection and loss. Consequently, most data on the safety and efficacy of ICIs in SOTRs are derived from case series and reports. Given the significant risks involved, alternative therapeutic options should be thoroughly discussed with patients before considering ICI therapy. This literature review aims to provide an overview of CSCC in SOTRs, with a specific emphasis on therapeutic and screening strategies, particularly highlighting immunotherapy.
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Affiliation(s)
- Ann-Kristin Struckmeier
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
| | - Martin Gosau
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
| | - Ralf Smeets
- Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; Department of Oral and Maxillofacial Surgery, Division of Regenerative Orofacial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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5
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Gabriel EM, Necela B, Bahr D, Vivekanandhan S, Shreeder B, Bagaria S, Knutson KL. Expression of c-erb-B2 oncoprotein as a neoantigen strategy to repurpose anti-neu antibody therapy in a model of melanoma. Sci Rep 2024; 14:24545. [PMID: 39427012 PMCID: PMC11490618 DOI: 10.1038/s41598-024-76209-z] [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: 03/01/2024] [Accepted: 10/11/2024] [Indexed: 10/21/2024] Open
Abstract
In this study, we tested a novel approach of "repurposing" a biomarker typically associated with breast cancer for use in melanoma. HER2/neu is a well characterized biomarker in breast cancer for which effective anti-HER2/neu therapies are readily available. We constructed a lentivirus encoding c-erb-B2, an animal (rat) homolog to HER2/neu. This was used to transfect B16 melanoma in vitro for use in an orthotopic preclinical mouse model, which resulted in expression of rat c-erb-B2 as a neoantigen target for anti-c-erb-B2 monoclonal antibody (7.16.4). The c-erb-B2-expressing melanoma was designated B16/neu. 7.16.4 produced statistically significant in vivo anti-tumor responses against B16/neu. This effect was mediated by NK-cell antibody-dependent cell-mediated cytotoxicity. To further model human melanoma (which expresses < 5% HER2/neu), our c-erb-B2 encoding lentivirus was used to inoculate naïve (wild-type) B16 tumors in vivo, resulting in successful c-erb-B2 expression. When combined with 7.16.4, anti-tumor responses were again demonstrated where approximately 40% of mice treated with c-erb-B2 lentivirus and 7.16.4 achieved complete clinical response and long-term survival. For the first time, we demonstrated a novel strategy to repurpose c-erb-B2 as a neoantigen target for melanoma. Our findings are particularly significant in the contemporary setting where newer anti-HER2/neu antibody-drug therapies have shown increased efficacy.
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MESH Headings
- Animals
- Receptor, ErbB-2/metabolism
- Receptor, ErbB-2/immunology
- Receptor, ErbB-2/genetics
- Receptor, ErbB-2/antagonists & inhibitors
- Mice
- Humans
- Rats
- Antigens, Neoplasm/immunology
- Antigens, Neoplasm/genetics
- Melanoma, Experimental/immunology
- Melanoma, Experimental/therapy
- Antibodies, Monoclonal/pharmacology
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal/immunology
- Cell Line, Tumor
- Female
- Disease Models, Animal
- Lentivirus/genetics
- Melanoma/therapy
- Melanoma/immunology
- Melanoma/drug therapy
- Melanoma/genetics
- Mice, Inbred C57BL
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Affiliation(s)
- Emmanuel M Gabriel
- Division of Surgical Oncology, Department of General Surgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
| | - Brian Necela
- Department of Immunology, Mayo Clinic, Jacksonville, FL, USA
| | - Deborah Bahr
- Department of Immunology, Mayo Clinic, Jacksonville, FL, USA
| | | | - Barath Shreeder
- Department of Immunology, Mayo Clinic, Jacksonville, FL, USA
| | - Sanjay Bagaria
- Division of Surgical Oncology, Department of General Surgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Keith L Knutson
- Department of Immunology, Mayo Clinic, Jacksonville, FL, USA
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6
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Shawer R, Solomon A. Adverse effects of anti-cancer biologics on the ocular surface. Curr Opin Allergy Clin Immunol 2024; 24:390-396. [PMID: 38963724 DOI: 10.1097/aci.0000000000001007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
PURPOSE OF REVIEW Cancer immunotherapy is one of the most emerging and rapidly growing fields.Ocular side effects associated with these therapies are common and can be present in up to 70% of patients.The cornea may be involved in different pathogenic mechanisms triggered by different immunotherapeutic agents, and corneal disease varies from mild symptoms to severe corneal ulceration and melting with visual loss.We aimed to review the incidence, mechanism, and management of ocular surface side effects in cancer patients receiving immunotherapy. RECENT FINDINGS With the recent use of immunotherapeutic agents in cancer patients, in particular immune checkpoint inhibitors (ICIs) and epidermal growth factor receptor (EGFR) inhibitors, ocular surface and corneal involvement are common side effects.These patients can be at risk of sight threatening complications that warrant prompt diagnosis and careful monitoring and management. SUMMARY Immunotherapy- related corneal complications in cancer patients are associated with a decreased quality of life. Prompt recognition and an interdisciplinary approach between ophthalmologists and oncologists are crucial to handle immune related ocular adverse events in these patients, in order to maintain ocular surface integrity and avoid a vision threatening complication.
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Affiliation(s)
- Riham Shawer
- Department of Ophthalmology, Hadassah-Hebrew University Medical Centre
- St. John Eye Hospital, Jerusalem, Israel
| | - Abraham Solomon
- Department of Ophthalmology, Hadassah-Hebrew University Medical Centre
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7
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Martin SP, Mehta N, Emamaullee J. Immune checkpoint inhibitors in liver transplantation: Current practice, challenges, and opportunities. Liver Transpl 2024; 30:742-752. [PMID: 38345379 DOI: 10.1097/lvt.0000000000000350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 02/08/2024] [Indexed: 06/15/2024]
Abstract
Immune checkpoint inhibitors are becoming a mainstay of cancer treatment. While first studied and approved for patients with unresectable disease, due to their efficacy, they are becoming increasingly used in the perioperative period across many cancer types. In patients with HCC, immune checkpoint inhibitors have now become the standard of care in the advanced setting and have shown promising results in the adjuvant setting after liver resection. While these drugs continue to show promise, their role in the peritransplant setting still remains a question. In this review, we explore the current use of this class of medications in patients with HCC, as well as the immunologic role of the pathways that they inhibit. We also identify potential for future research opportunities to better understand the role of these medications.
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Affiliation(s)
- Sean P Martin
- Department of Surgery, Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Surgery, Division of Transplantation, Penn State Health Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Neil Mehta
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, UCSF, San Francisco, California, USA
| | - Juliet Emamaullee
- Department of Surgery, Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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8
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Zhou K, Gong D, Han Y, Huang W. Role of brentuximab vedotin plus sirolimus in the treatment of classical Hodgkin lymphoma type post-transplant lymphoproliferative disorder: a case-based review. Ann Hematol 2024; 103:2207-2213. [PMID: 37749317 DOI: 10.1007/s00277-023-05446-5] [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: 04/01/2023] [Accepted: 09/06/2023] [Indexed: 09/27/2023]
Abstract
Post-transplant lymphoproliferative disorder (PTLD) is a common secondary malignancy after transplantation, which has been recognized as a life-threatening complication. Hodgkin lymphoma (HL)-type PTLD is the rarest of four subtypes of PTLD, which has no treatment guideline due to its rarity. HL-type PTLD includes classical HL-type PTLD (cHL-PTLD) and HL-like PTLD. In our study, we reported the case of successful treatment using brentuximab vedotin (BV) plus sirolimus for a patient with classical HL-type PTLD in detail. Lymph node biopsy showed a picture of classical HL with mixed cellularity subtype, and immunophenotyping suggested CD30 strong positivity. Due to his impaired physical condition, we decided against intensive chemotherapy and started BV treatment with immunosuppressive agents switched to sirolimus. The 66-year-old patient with cHL-PTLD had achieved a durable complete remission for over a 1-year follow-up period. Additionally, we analyzed the clinical profile and outcomes in PTLD patients who used BV monotherapy or combined therapy by literature review. In summary, this case-based review might provide clues that treatment of cHL-PTLD with new modalities such as BV monotherapy or combination therapy, together with improvements in the immunosuppressive regimens like sirolimus, might be a feasible and chemotherapy-free approach, but warrants further evaluation in a larger patient cohort.
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Affiliation(s)
- Kuangguo Zhou
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Duanhao Gong
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yunfeng Han
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Huang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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9
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Aldarayseh M, Sodhi SS, Musleh G, Kumar D, Cholankeril M. Unforeseen Complications of Pembrolizumab in Breast Reconstruction Post-Mastectomy. Eur J Case Rep Intern Med 2024; 11:004675. [PMID: 38984194 PMCID: PMC11229478 DOI: 10.12890/2024_004675] [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: 05/30/2024] [Accepted: 06/10/2024] [Indexed: 07/11/2024] Open
Abstract
A 53-year-old post-menopausal Indian female presented with invasive ductal carcinoma, treated with neoadjuvant chemotherapy and pembrolizumab due to a PD-L1 combined positive score of 5. Following a right mastectomy and axillary dissection, she received a breast expander and AlloDerm™ graft. After resuming pembrolizumab and paclitaxel postoperatively, she developed severe breast redness and high-grade fever, necessitating expander removal due to suspected pembrolizumab-induced complications. This case underscores the unique and severe adverse effects of pembrolizumab on breast reconstruction, highlighting the need for careful monitoring and management in patients undergoing similar treatments. LEARNING POINTS Among patients with early triple-negative breast cancer, the combination of pembrolizumab with neoadjuvant chemotherapy enhances outcomes compared to chemotherapy alone.Early recognition is essential for managing pembrolizumab-induced complications, as demonstrated by the need for expander removal and debridement in this case.The unique adverse effects observed in this case underscore the importance of tailoring cancer treatment plans to individual patients, taking into account the potential risks associated with immunotherapy in the context of reconstructive surgery.
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Affiliation(s)
- Murad Aldarayseh
- Internal Medicine Department, RWJ Barnabas Health/Trinitas Regional Medical Center, Elizabeth, USA
| | - Sohail Singh Sodhi
- Internal Medicine Department, RWJ Barnabas Health/Trinitas Regional Medical Center, Elizabeth, USA
| | - Gamal Musleh
- Internal Medicine Department, RWJ Barnabas Health/Trinitas Regional Medical Center, Elizabeth, USA
| | - Dyuti Kumar
- St George's University School of Medicine, Grenada, West Indies
| | - Michelle Cholankeril
- Internal Medicine Department, RWJ Barnabas Health/Trinitas Regional Medical Center, Elizabeth, USA
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10
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Singal AG, Yarchoan M, Yopp A, Sapisochin G, Pinato DJ, Pillai A. Neoadjuvant and adjuvant systemic therapy in HCC: Current status and the future. Hepatol Commun 2024; 8:e0430. [PMID: 38829199 PMCID: PMC11150030 DOI: 10.1097/hc9.0000000000000430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 01/13/2024] [Indexed: 06/05/2024] Open
Abstract
Surgical therapies in patients with early-stage HCC can afford long-term survival but are often limited by the continued risk of recurrence, underscoring an interest in (neo)adjuvant strategies. Prior attempts at adjuvant therapy using tyrosine kinase inhibitors failed to yield significant improvements in recurrence-free survival or overall survival. Advances in the efficacy of systemic therapy options, including the introduction of immune checkpoint inhibitors, have fueled renewed interest in this area. Indeed, the IMBrave050 trial recently demonstrated significant improvements in recurrence-free survival with 1 year of adjuvant atezolizumab plus bevacizumab in high-risk patients undergoing surgical resection or ablation, with several other ongoing trials in this space. There is a strong rationale for consideration of the administration of these therapies in the neoadjuvant setting, supported by early clinical data demonstrating high rates of objective responses, although larger trials examining downstream outcomes are necessary, particularly considering the possible risks of this strategy. In parallel, there has been increased interest in using systemic therapies as a bridging or downstaging strategy for liver transplantation. Current data suggest the short-term safety of this approach, with acceptable rates of rejection, so immunotherapy is not considered a contraindication to transplant; however, larger studies are needed to evaluate the incremental value of this approach over locoregional therapy. Conversely, the use of immunotherapy is currently discouraged after liver transplantation, given the high risk of graft rejection and death. The increasing complexity of HCC management and increased consideration of (neo)adjuvant strategies highlight the critical role of multidisciplinary care when making these decisions.
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Affiliation(s)
- Amit G. Singal
- Department of Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Mark Yarchoan
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Adam Yopp
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Gonzalo Sapisochin
- Department of Surgery, University of Toronto and University Health Network, Toronto, Ontario, Canada
| | - David J. Pinato
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK
- Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale, Novara, Italy
| | - Anjana Pillai
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
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11
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Cillo U, Carraro A, Avolio AW, Cescon M, Di Benedetto F, Giannelli V, Magistri P, Nicolini D, Vivarelli M, Lanari J. Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT). Updates Surg 2024; 76:725-741. [PMID: 38713396 DOI: 10.1007/s13304-024-01845-z] [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: 07/13/2023] [Accepted: 07/31/2023] [Indexed: 05/08/2024]
Abstract
Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result. However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients. The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed. The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.
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Affiliation(s)
- Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, General Surgery 2 Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Padua University Hospital, Via Giustiniani 2, 34128, Padua, PD, Italy.
| | - Amedeo Carraro
- Liver Transplant Unit, Department of Surgery and Oncology, University Hospital Trust of Verona, Verona, Italy
| | - Alfonso W Avolio
- Department of General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Matteo Cescon
- General Surgery and Transplantation Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria-Policlinico S.Orsola-Malpighi, Bologna, Italy
| | - Fabrizio Di Benedetto
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Valerio Giannelli
- Liver Unit, Department of Liver Transplant, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Paolo Magistri
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Daniele Nicolini
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Riuniti Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Marco Vivarelli
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Riuniti Hospital, Polytechnic University of Marche, Ancona, Italy
| | - Jacopo Lanari
- Department of Surgical, Oncological and Gastroenterological Sciences, General Surgery 2 Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Padua University Hospital, Via Giustiniani 2, 34128, Padua, PD, Italy
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12
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Gabriel EM, Necela B, Bahr D, Vivekanandhan S, Shreeder B, Bagaria S, Knutson KL. Expression of c-erb-B2 oncoprotein as a neoantigen strategy to repurpose anti-neu antibody therapy in a model of melanoma. RESEARCH SQUARE 2024:rs.3.rs-4004491. [PMID: 38645250 PMCID: PMC11030526 DOI: 10.21203/rs.3.rs-4004491/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/23/2024]
Abstract
In this study, we tested a novel approach of "repurposing" a biomarker typically associated with breast cancer for use in melanoma. HER2/neu is a well characterized biomarker in breast cancer for which effective anti-HER2/neu therapies are readily available. We constructed a lentivirus encoding c-erb-B2 (the animal homolog to HER2/neu). This was used to transfect B16 melanoma in vitro for use in an orthotopic preclinical mouse model, which resulted in expression of c-erb-B2 as a neoantigen target for anti-c-erb-B2 monoclonal antibody (7.16.4). The c-erb-B2-expressing melanoma was designated B16/neu. 7.16.4 produced statistically significant in vivo anti-tumor responses against B16/neu. This effect was mediated by NK-cell antibody-dependent cell-mediated cytotoxicity. To further model human melanoma (which expresses <5% HER2/neu), our c-erb-B2 encoding lentivirus was used to inoculate naïve (wild-type) B16 tumors in vivo, resulting in successful c-erb-B2 expression. When combined with 7.16.4, anti-tumor responses were again demonstrated where approximately 40% of mice treated with c-erb-B2 lentivirus and 7.16.4 achieved complete clinical response and long-term survival. For the first time, we demonstrated a novel strategy to repurpose c-erb-B2 as a neoantigen target for melanoma. Our findings are particularly significant in the contemporary setting where newer anti-HER2/neu antibody-drug candidates have shown increased efficacy.
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13
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Jang HJ, Yoon JK. The Role of Vasculature and Angiogenic Strategies in Bone Regeneration. Biomimetics (Basel) 2024; 9:75. [PMID: 38392121 PMCID: PMC10887147 DOI: 10.3390/biomimetics9020075] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 01/18/2024] [Accepted: 01/22/2024] [Indexed: 02/24/2024] Open
Abstract
Bone regeneration is a complex process that involves various growth factors, cell types, and extracellular matrix components. A crucial aspect of this process is the formation of a vascular network, which provides essential nutrients and oxygen and promotes osteogenesis by interacting with bone tissue. This review provides a comprehensive discussion of the critical role of vasculature in bone regeneration and the applications of angiogenic strategies, from conventional to cutting-edge methodologies. Recent research has shifted towards innovative bone tissue engineering strategies that integrate vascularized bone complexes, recognizing the significant role of vasculature in bone regeneration. The article begins by examining the role of angiogenesis in bone regeneration. It then introduces various in vitro and in vivo applications that have achieved accelerated bone regeneration through angiogenesis to highlight recent advances in bone tissue engineering. This review also identifies remaining challenges and outlines future directions for research in vascularized bone regeneration.
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Affiliation(s)
- Hye-Jeong Jang
- Department of Systems Biotechnology, Chung-Ang University, Anseong-si 17546, Gyeonggi-do, Republic of Korea
| | - Jeong-Kee Yoon
- Department of Systems Biotechnology, Chung-Ang University, Anseong-si 17546, Gyeonggi-do, Republic of Korea
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14
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Venkataraman K, Salehi T, Carroll RP. Immune Checkpoint Inhibitors in Recipients of Renal Allografts. Semin Nephrol 2024; 44:151500. [PMID: 38548484 DOI: 10.1016/j.semnephrol.2024.151500] [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: 06/30/2024]
Abstract
Kidney transplant recipients are at increased risk of malignancy as a result of immunosuppression and are increasingly exposed to checkpoint inhibitors (CPIs). However, CPI therapy can precipitate allograft rejection. This review aims to summarize the current literature describing the epidemiology, immunological mechanisms, diagnosis, and treatment of CPI-associated allograft rejection.Initial studies of CPIs suggested allograft rejection post commencement of CPIs occured commonly (40-60%), occurring between 2 and 6 weeks after CPI initiation, with a cancer response rate approaching 50%. More recent studies with predefined, structured immunosuppressive regimens have seen rejection rates of 0-12.5%, with rejection occurring later. Allograft biopsy remains the mainstay of diagnosis; however, noninvasive tools are emerging, including donor-derived cell-free DNA, urinary chemokine assessment, and defining alloreactive T-cell clones prior to or during CPI therapy.
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Affiliation(s)
- Karthik Venkataraman
- Central and Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, Australia
| | - Tania Salehi
- Central and Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, Australia
| | - Robert P Carroll
- Central and Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, Australia; Australian Red Cross Lifeblood Service, Department of Health Sciences, University of South Australia, Adelaide, Australia.
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15
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Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, van Akkooi A, Bataille V, Bastholt L, Dreno B, Dummer R, Fargnoli MC, Forsea AM, Harwood CA, Hauschild A, Hoeller C, Kandolf-Sekulovic L, Kaufmann R, Kelleners-Smeets NW, Lallas A, Leiter U, Malvehy J, Del Marmol V, Moreno-Ramirez D, Pellacani G, Peris K, Saiag P, Tagliaferri L, Trakatelli M, Ioannides D, Vieira R, Zalaudek I, Arenberger P, Eggermont AMM, Röcken M, Grob JJ, Lorigan P. European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment-Update 2023. Eur J Cancer 2023; 193:113252. [PMID: 37708630 DOI: 10.1016/j.ejca.2023.113252] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 07/18/2023] [Indexed: 09/16/2023]
Abstract
In order to update recommendations on treatment, supportive care, education, and follow-up of patients with invasive cutaneous squamous cell carcinoma (cSCC), a multidisciplinary panel of experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS), the European Academy of Dermatology and Venereology (EADV), and the European Organisation of Research and Treatment of Cancer (EORTC) was formed. Recommendations were based on an evidence-based literature review, guidelines, and expert consensus. Treatment recommendations are presented for common primary cSCC (low risk, high risk), locally advanced cSCC, regional metastatic cSCC (operable or inoperable), and distant metastatic cSCC. For common primary cSCC, the first-line treatment is surgical excision with postoperative margin assessment or micrographically controlled surgery. Achieving clear surgical margins is the most important treatment consideration for patients with cSCCs amenable to surgery. Regarding adjuvant radiotherapy for patients with high-risk localised cSCC with clear surgical margins, current evidence has not shown significant benefit for those with at least one high-risk factor. Radiotherapy should be considered as the primary treatment for non-surgical candidates/tumours. For cSCC with cytologically or histologically confirmed regional nodal metastasis, lymph node dissection is recommended. For patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or radiotherapy, anti-PD-1 agents are the first-line systemic treatment, with cemiplimab being the first approved systemic agent for advanced cSCC by the Food and Drugs Administration/European Medicines Agency. Second-line systemic treatments for advanced cSCC, include epidermal growth factor receptor inhibitors (cetuximab) combined with chemotherapy or radiotherapy. Multidisciplinary board decisions are mandatory for all patients with advanced cSCC, considering the risks of toxicity, the age and frailty of patients, and co-morbidities, including immunosuppression. Patients should be engaged in informed, shared decision-making on management and be provided with the best supportive care to improve symptom management and quality of life. The frequency of follow-up visits and investigations for subsequent new cSCC depends on underlying risk characteristics.
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Affiliation(s)
- Alexander J Stratigos
- First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece.
| | - Claus Garbe
- Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | - Clio Dessinioti
- First Department of Dermatology-Venereology, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece
| | - Celeste Lebbe
- Université Paris Cite, Dermato-Oncology AP-HP Hôpital Saint Louis, Cancer Institute APHP. Nord-Université Paris Cite, INSERM U976, Paris, France
| | - Alexander van Akkooi
- Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Melanoma Institute Australia, Sydney, New South Wales, Australia
| | | | - Lars Bastholt
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Brigitte Dreno
- Nantes Université, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes, France
| | - Reinhard Dummer
- Skin Cancer Centre at University Hospital, Zurich, Switzerland
| | - Maria Concetta Fargnoli
- Dermatology Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Ana Maria Forsea
- Carol Davila University of Medicine and Pharmacy Bucharest, Department of Oncologic Dermatology, Elias University Hospital Bucharest, Bucharest, Romania
| | - Catherine A Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Axel Hauschild
- Department of Dermatology, University Hospital (UKSH), Kiel, Germany
| | - Christoph Hoeller
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | | | - Roland Kaufmann
- Department of Dermatology, Venereology and Allergology, Frankfurt University Hospital, Frankfurt, Germany
| | - Nicole Wj Kelleners-Smeets
- GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Dermatology, Maastricht University Medical Centre+, Maastricht University, Maastricht, the Netherlands
| | - Aimilios Lallas
- First Department of Dermatology, Aristotle University, Thessaloniki, Greece
| | - Ulrike Leiter
- Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | - Josep Malvehy
- Dermatology Department of Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBER de enfermedades raras, Instituto Carlos III, Barcelona, Spain
| | - Veronique Del Marmol
- Department of Dermatology, University Hospital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - David Moreno-Ramirez
- Department of Medical and Surgical Dermatology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain
| | | | - Ketty Peris
- UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy; Dermatologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Philippe Saiag
- Department of General and Oncologic Dermatology, Ambroise-Paré hospital, APHP, and EA 4340 'Biomarkers in Cancerology and Hemato-oncology', UVSQ, Université Paris-Saclay, Boulogne-Billancourt, France
| | - Luca Tagliaferri
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
| | - Myrto Trakatelli
- Department of Dermatology, Papageorgiou Hospital, Aristotle University Department of Medicine, Thessaloniki, Greece
| | | | - Ricardo Vieira
- Department of Dermatology, Coimbra Hospital and University Centre, Coimbra, Portugal
| | - Iris Zalaudek
- Department of Dermatology, University of Trieste, Trieste, Italy
| | - Petr Arenberger
- Department of Dermatovenereology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Alexander M M Eggermont
- University Medical Center Utrecht and Princess Máxima Center, Utrecht, the Netherlands; Comprehensive Cancer Center Munich, Technical University Munich and Ludwig Maximilian University, Munich, Germany
| | - Martin Röcken
- Centre for Dermatooncology, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | | | - Paul Lorigan
- Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, UK
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16
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Ji S, Liu H, Pachella L, Stephenson RD, Groisberg R, Weiss SA. Use of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies. FRONTIERS IN TRANSPLANTATION 2023; 2:1284740. [PMID: 38993910 PMCID: PMC11235332 DOI: 10.3389/frtra.2023.1284740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/13/2023] [Indexed: 07/13/2024]
Abstract
Background Immune checkpoint inhibitors (ICI) are standard of care therapy for patients with cutaneous malignancies, the most frequently diagnosed cancers in solid organ transplant (SOT) recipients. The activity and rate of allograft rejection in SOT recipients with advanced skin cancers treated with ICI is understudied. Methods We conducted a retrospective analysis of SOT recipients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), and merkel cell carcinoma (MCC) who were treated with ICI. Unpublished cases from our institution and published cases from the literature were aggregated. Demographics, type of immunosuppressive therapy, type of ICI(s) administered, prior systemic therapies, tumor response to ICI, and evidence of organ rejection and/or failure were recorded. Objective response rates (ORR) and rates of graft rejection and failure are reported. Results Ninety patients were identified; four patients from our institution and 86 unique patients from a literature review. ORR to first-line ICI for the entire cohort was 41.1% (37/90). ORR by tumor type was 31% (18/58), 64.3% (18/28), and 25.0% (1/4) for melanoma, cSCC, and MCC, respectively. The rate of graft rejection was 37.8% (34/90) with 61.8% (21/34) of these cases progressing to graft failure. Number of immunosuppressive agents (0, 1, 2, or 3) was inversely associated with rate of graft failure. Conclusions In this retrospective analysis, ICIs demonstrate clinical activity in SOT recipients with cutaneous malignancies; however, the rate of graft rejection is high. Treatment plans should be individualized through thorough interdisciplinary discussion. Immunosuppressive modifications may be considered prior to starting treatment, but when feasible, enrollment on clinical trials is preferred.
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Affiliation(s)
- Stephanie Ji
- Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
| | - Hao Liu
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, New Brunswick, NJ, United States
| | - Laura Pachella
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
| | - Ryan D Stephenson
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
| | - Roman Groisberg
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
| | - Sarah A Weiss
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States
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17
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Lorini L, Alberti A, Bossi P. Advanced Cutaneous Squamous Cell Carcinoma Management in Immunotherapy Era: Achievements and New Challenges. Dermatol Pract Concept 2023; 13:dpc.1304a251. [PMID: 37992352 PMCID: PMC10656166 DOI: 10.5826/dpc.1304a251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/09/2023] [Indexed: 11/24/2023] Open
Abstract
Introduction of immunotherapy (IT) has radically changed the therapeutic scenario in patients affected by locally advanced and/or metastatic cutaneous squamous cell carcinoma (cSCC) patients. If it is well consolidated the role of immunotherapy in the setting of a disease not amenable to curative surgery and/or radiation, how to integrate immune checkpoint inhibitors in the curative setting is still under evaluation. Surgery combined or not with adjuvant radiotherapy remains the mainstay of curative treatment in localized cSCC; however, promising data with neoadjuvant or perioperative immunotherapy could pave the way towards treatment de-escalation according to the response achieved. On the other side, data on adjuvant treatment with pembrolizumab and cemiplimab after surgery and radiation are still awaited. Several questions related to the activity and the safety of immunotherapy in the real-world setting still remain without answer, and several points need to be better explored. In the current review we will explore the updated literature on the use of immunotherapy in cSCC, and we will show the current challenges in its use.
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Affiliation(s)
- Luigi Lorini
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Andrea Alberti
- Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy
| | - Paolo Bossi
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
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18
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Cui X, Yan C, Xu Y, Li D, Guo M, Sun L, Zhu Z. Allograft rejection following immune checkpoint inhibitors in solid organ transplant recipients: A safety analysis from a literature review and a pharmacovigilance system. Cancer Med 2023; 12:5181-5194. [PMID: 36504294 PMCID: PMC10028127 DOI: 10.1002/cam4.5394] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/13/2022] [Accepted: 10/21/2022] [Indexed: 12/14/2022] Open
Abstract
AIM This study aimed to systematically characterize transplant rejection after immune checkpoint inhibitors (ICIs) initiation in solid organ transplant recipients (SOTRs). METHODS Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database and case reports in the literature. Disproportionality analysis including information component and reported odds ratio (ROR) was performed to access potential risk signals. RESULTS A total of 168 patients with transplant rejection after ICIs usage were identified in the FAERS database, and 89 cases were identified in the literature review. ICIs were significantly associated with transplant rejection (ROR025 : 2.2). A strong risk signal was found for combination therapy with pembrolizumab and ipilimumab compared to monotherapy. CONCLUSION Immune checkpoint inhibitors were significantly associated with transplant rejection in SOTRs.
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Affiliation(s)
- Xiangli Cui
- Pharmacy Department of Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Cilin Yan
- School of Automation Science and Electrical Engineering, Beihang University, Beijing, China
| | - Ye Xu
- Pharmacy Department of Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Dandan Li
- Pharmacy Department of Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Mingxing Guo
- Pharmacy Department of Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Liying Sun
- Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhijun Zhu
- Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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19
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Zhang P, Zhu G, Li L, Lai G, Wang Z, Sun C, Xia W, Wu L. Immune checkpoint inhibitor therapy for malignant tumors in liver transplantation recipients: A systematic review of the literature. Transplant Rev (Orlando) 2022; 36:100712. [PMID: 35870411 DOI: 10.1016/j.trre.2022.100712] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/29/2022] [Accepted: 07/01/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Treatment for de novo or recurrent tumors of liver transplantation (LT) recipients is challenging and immune checkpoint inhibitor (ICI) is recently well developed and could be a potentially effective option for this population. There remains limited evidence on the safety and efficacy of ICI therapy in LT recipients. METHODS A systematic literature search was conducted on PubMed database through April 1, 2022, to identify publications reporting ICI treatment for malignant tumors in LT recipients. We summarized the allograft rejection, mortality, and tumor response of ICI treatment. RESULTS 24 articles with 41 LT recipients were identified. The age of LT recipients ranged from 14 to 78, 76.2% were male, 56.1% had recurrent HCC, and 87.8% received anti-PD-1 therapy. Allograft rejection occurred in 31.7% of patients, death was reported in 46.3% and 6 cases died secondary to allograft rejection. Progressive disease rate of this population was 48.8% and 10 patients responded to immunotherapy. Half of recipients with positive PD-L1 staining (4/8) experienced allograft rejection. CONCLUSIONS ICI therapy has potential therapeutic value on malignant tumors for LT recipients, accompanied by a high rate of allograft rejection and mortality. PD-L1 expression, type of ICI, and immunosuppression agent should be taken into consideration before initiation of immunotherapy. Further studies are needed to optimize this anticancer treatment approach in these patients.
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Affiliation(s)
- Pinzhe Zhang
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Shantou University Medical College, Shantou, China
| | - Guanghao Zhu
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Leping Li
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Shantou University Medical College, Shantou, China
| | - Guanzhi Lai
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Shantou University Medical College, Shantou, China
| | - Zekang Wang
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Chengjun Sun
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Wuzheng Xia
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Linwei Wu
- Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
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20
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Immune checkpoint blockade for organ-transplant recipients with cancer: A review. Eur J Cancer 2022; 175:326-335. [DOI: 10.1016/j.ejca.2022.08.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/02/2022] [Accepted: 08/05/2022] [Indexed: 11/24/2022]
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An J, Han S, Kim HI, Shim JH. Ranking of transarterial and targeted therapies for advanced hepatocellular carcinoma in the era of immuno-oncology: A network meta-analysis of randomized sorafenib-controlled trials. Hepatol Commun 2022; 6:2886-2900. [PMID: 35785525 PMCID: PMC9512463 DOI: 10.1002/hep4.2025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 03/09/2022] [Accepted: 05/29/2022] [Indexed: 11/09/2022] Open
Abstract
To date, no studies have compared the new first-line atezolizumab+bevacizumab with transarterial therapies combined with the prior standard-of-care, sorafenib, in patients with advanced hepatocellular carcinoma (HCC). We compared and ranked all relevant transarterial and targeted treatments competing with atezolizumab+bevacizumab for such disease, based on direct and indirect evidence. This network meta-analysis was conducted as a systematic review of phase 2 and 3 randomized sorafenib-controlled trials investigating systemic treatment strategies for HCCs unsuitable for or that progressed after surgery or locoregional treatments as first-line option published between 2008 and 2021. We ranked the treatments based on overall survival (OS) as the primary outcome, together with progression-free survival (PFS) and grade 3-4 adverse events. Subgroup analyses were also implemented to estimate intervention efficacies in particular groups. We identified 3451 publications, 15 trials consisting of 7158 patients, using 14 different therapies including combinations of sorafenib with transarterial chemoembolization (TACE), hepatic arterial chemoinfusion, and radioembolization. Regarding OS, atezolizumab+bevacizumab was the only regimen significantly superior to sorafenib (hazard ratio 0.42; 95% confidence interval [CI] 0.25-0.70), and it ranked first. This combination was also the best in the PFS analysis (0.59; 0.47-0.74), followed by lenvatinib (0.66; 0.57-0.76) and TACE+sorafenib (0.73; 0.59-0.91); all had significantly better outcomes than sorafenib alone. TACE+sorafenib (0.52; 0.27-1.00) was ranked first based on OS in a subset with portal invasion, but not in the metastatic series, with atezolizumab+bevacizumab second (0.58; 0.38-0.89). Lenvatinib (odds ratio 1.76; 95% CI 1.35-2.30) and TACE+sorafenib (2.02; 1.23-3.32), but not atezolizumab+bevacizumab (1.38; 0.93-2.05), were significantly less safe than sorafenib monotherapy. Conclusion: Our results indicate that atezolizumab+bevacizumab is the best first-line clinically relevant systemic modality in advanced HCC. TACE+sorafenib may also be considered for the disease with portal invasion. (PROSPERO No. CRD42021250701).
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Affiliation(s)
- Jihyun An
- Gastroenterology and HepatologyHanyang University College of MedicineGuriRepublic of Korea
| | - Seungbong Han
- Department of BiostatisticsCollege of MedicineKorea UniversitySeoulRepublic of Korea
| | - Ha Il Kim
- Department of GastroenterologyKyung Hee University Hospital at GangdongSeoulRepublic of Korea
| | - Ju Hyun Shim
- Asan Liver CenterAsan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
- Department of GastroenterologyAsan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
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22
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Moshirfar M, Basharat NF, Seitz TS, Ply BK, Ronquillo YC, Hoopes PC. Corneal Transplant Rejections in Patients Receiving Immune Checkpoint Inhibitors. J Clin Med 2022; 11:jcm11195647. [PMID: 36233514 PMCID: PMC9572806 DOI: 10.3390/jcm11195647] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 09/14/2022] [Accepted: 09/20/2022] [Indexed: 11/17/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) are antibodies that target and block immune checkpoints. These biologics were initially approved by the United States Food and Drug Administration (US FDA) in 2011 for the management of melanoma. Since then, the use of ICI therapy has increased, with many new medications on the market that treat approximately 50 types of cancers. Patients receiving this therapy are at an increased risk for transplant rejection, including corneal rejection. Ophthalmologists must be aware of individuals receiving ICI therapy as it may be a relative contraindication for patients with a history of corneal transplantation. Patients on ICIs may also experience ocular side effects, including uveitis, dry eye, and inflammation, while on checkpoint inhibitor therapy. This commentary discusses the current understanding of immune checkpoint inhibitors, their mechanism of action, their ocular side effects, and their role in corneal transplant rejection.
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Affiliation(s)
- Majid Moshirfar
- Hoopes Vision Research Center, Hoopes Vision, 11820 S. State St. #200, Draper, UT 84020, USA
- John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
- Utah Lions Eye Bank, Murray, UT 84107, USA
- Correspondence: ; Tel.: +1-801-568-0200
| | - Noor F. Basharat
- University of Arizona College of Medicine—Phoenix, Phoenix, AZ 85004, USA
| | - Tanner S. Seitz
- Midwestern University Arizona College of Osteopathic Medicine, Glendale, AZ 85308, USA
| | - Briana K. Ply
- Hoopes Vision Research Center, Hoopes Vision, 11820 S. State St. #200, Draper, UT 84020, USA
| | - Yasmyne C. Ronquillo
- Hoopes Vision Research Center, Hoopes Vision, 11820 S. State St. #200, Draper, UT 84020, USA
| | - Phillip C. Hoopes
- Hoopes Vision Research Center, Hoopes Vision, 11820 S. State St. #200, Draper, UT 84020, USA
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Serkies K, Dębska-Ślisień A, Kowalczyk A, Lizakowski S, Małyszko J. Malignancies in adult kidney transplant candidates and recipients: current status. Nephrol Dial Transplant 2022:6674222. [PMID: 35998321 DOI: 10.1093/ndt/gfac239] [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: 11/12/2022] Open
Abstract
Posttransplant malignancies, particularly recurrent and de novo, in solid organs including kidney transplant recipients (KTRs) are a significant complication associated with substantial mortality, largely attributed to long-term immunosuppression necessary to maintain allograft tolerance. Older age at transplantation and oncogenic virus infection along with pretransplant malignancies are among the main factors contributing to the risk of cancer in this population. As the mean age of transplant candidates rises, the rate of transplant recipients with pretransplant malignancies also increases. The eligibility criteria for transplantation in patients with prior cancer have recently changed. The overall risk of posttransplant malignancies is at least double after transplantation including KTRs relative to the general population, most pronounced for skin cancers associated with UV radiation and virally-mediated tumors. The risk of renal cell carcinoma is specifically increased in the kidney transplant population. The therapy of cancer in transplant patients is associated with risk of higher toxicity, and graft rejection and/or impairment, which poses a unique challenge in the management. Reduction of immunosuppression and the use of mTOR inhibitors are common after cancer diagnosis, although optimal immunosuppression for transplant recipients with cancer remains undefined. Suboptimal cancer treatment contributing to a worse prognosis has been reported for malignancies in this population. In this article, we focus on the prevalence and outcomes of posttransplant malignancies, cancer therapy including a short overview of immunotherapy, cancer screening and prevention strategies, and immunosuppression as a cancer risk factor. The 2020/2021 recommendations of the Kidney Diseases Improving Global Outcome (KDIGO) and American Society of Transplantation (AST) for transplant candidates with a history of cancer are presented.
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Affiliation(s)
- Krystyna Serkies
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland
| | - Alicja Dębska-Ślisień
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland
| | - Anna Kowalczyk
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Poland
| | - Sławomir Lizakowski
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdańsk, Poland
| | - Jolanta Małyszko
- Department of Nephrology, Dialysis and Internal Medicine, Warsaw Medical University, Poland
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Park BC, Jung S, Chen ST, Dewan AK, Johnson DB. Challenging Dermatologic Considerations Associated with Immune Checkpoint Inhibitors. Am J Clin Dermatol 2022; 23:707-717. [PMID: 35708849 DOI: 10.1007/s40257-022-00706-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/16/2022] [Indexed: 11/25/2022]
Abstract
Immune checkpoint inhibitors have emerged as a new paradigm in oncologic care for many malignancies. However, nonspecific immune activation has led to "collateral damage" in the form of immune-related adverse events, with skin being a commonly affected organ. Cutaneous immune-related adverse events include a wide spectrum of clinical presentations and challenging considerations, often necessitating dermatology referral to support diagnosis and management, particularly for atypical presentations or more severe, cutaneous immune-related adverse events that may require specialized dermatologic evaluations including biopsy and histopathology. Close collaborations between oncologists and dermatologists may optimize clinical decision making in the following challenging management settings: non-steroidal therapies for corticosteroid-refractory, cutaneous immune-related adverse events, immune checkpoint inhibitor rechallenge, balancing cutaneous immune-related adverse events and treatments, and immune checkpoint inhibitors in patients with pre-existing autoimmune disease, skin conditions, and organ transplants. These complex clinical decisions that often lack rigorous data should be made in close collaboration with dermatologists to minimize unnecessary morbidity and mortality. This article provides a review of approaches to challenging dermatologic considerations associated with immune checkpoint inhibitor therapies.
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Affiliation(s)
- Benjamin C Park
- School of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Seungyeon Jung
- School of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Steven T Chen
- Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
| | - Anna K Dewan
- Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas B Johnson
- Department of Medicine, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN, 3723, USA.
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Dai T, Yang Q, Zhang Y, Ye L, Li H, Yi S, Liu W, Yang Y, Wang G. Camrelizumab (SHR-1210) treatment for recurrent hepatocellular carcinoma after liver transplant: A report of two cases. LIVER RESEARCH (BEIJING, CHINA) 2022; 6:111-115. [PMID: 39958628 PMCID: PMC11791810 DOI: 10.1016/j.livres.2021.06.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 05/16/2021] [Accepted: 06/17/2021] [Indexed: 12/26/2022]
Abstract
Immune checkpoint inhibitors are generally contraindicated for post-transplant patients. However, we report two patients with metastatic hepatocellular carcinoma (HCC) treated with camrelizumab (SHR-1210), an anti-programmed cell death 1 (PD-1) agent, after liver transplant. Before undergoing immunotherapy, both patients underwent liver allograft biopsy and obtained negative PD-L1 expression in tumor and liver graft specimens by immunohistochemistry. Then, camrelizumab (200 mg) was administered once every 3 weeks. During immunotherapy, the targeted therapy was continued, and the immunosuppression regimen was adjusted to a low-dose level. No graft rejection or other severe adverse reactions were observed. The disease remained stable (SD, mRECIST) for 3 months in one patient and 10 months in the other. Therefore, camrelizumab may have safety and potential benefits in advanced HCC after liver transplant.
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Affiliation(s)
- Tianxing Dai
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qing Yang
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yingcai Zhang
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Linsen Ye
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hua Li
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shuhong Yi
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wei Liu
- Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yang Yang
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guoying Wang
- Department of Hepatic Surgery, Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou, Guangdong, China
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Kamei J, Yokoyama H, Niki T, Suda R, Sugihara T, Fujisaki A, Ando S, Iwami D, Fujimura T. Complete response to pembrolizumab for metastatic urothelial carcinoma in the renal pelvis of allograft kidney. IJU Case Rep 2022; 5:199-202. [PMID: 35509786 PMCID: PMC9057750 DOI: 10.1002/iju5.12438] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 03/04/2022] [Accepted: 03/07/2022] [Indexed: 11/17/2022] Open
Abstract
Introduction We present a case of urothelial carcinoma in a renal allograft successfully treated with pembrolizumab. Case presentation A 39‐year‐old woman presented with nausea and anorexia 9 years after a renal transplantation. Positron emission tomography revealed a neoplasm of the renal pelvis of the allograft and multiple lymph nodes with peritoneal metastasis. A diagnosis of a non‐muscle‐invasive bladder tumor with peritoneal dissemination and jejunal metastasis of urothelial carcinoma was made. After five cycles of gemcitabine and carboplatin, the tumor progressed and pembrolizumab was administered. One week after the first dose, the allograft was rejected, necessitating arterial embolization. After the second cycle, the patient developed Stevens‐Johnson syndrome. After discontinuing pembrolizumab, positron emission tomography revealed no increased tumor activity. A complete response was achieved for 21 months without additional treatment. Conclusion Pembrolizumab was effective in treating urothelial carcinoma of the renal allograft; however, allograft rejection and loss should be considered.
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Affiliation(s)
- Jun Kamei
- Department of Urology Jichi Medical University Tochigi Japan
| | | | - Toshiro Niki
- Department of Integrative Pathology Jichi Medical University Tochigi Japan
| | - Ryosuke Suda
- Department of Renal Surgery and Transplantation Jichi Medical University Tochigi Japan
| | - Toru Sugihara
- Department of Urology Jichi Medical University Tochigi Japan
| | - Akira Fujisaki
- Department of Urology Jichi Medical University Tochigi Japan
| | - Satoshi Ando
- Department of Urology Jichi Medical University Tochigi Japan
| | - Daiki Iwami
- Department of Renal Surgery and Transplantation Jichi Medical University Tochigi Japan
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Alberti A, Bossi P. Immunotherapy for Cutaneous Squamous Cell Carcinoma: Results and Perspectives. Front Oncol 2022; 11:727027. [PMID: 35070956 PMCID: PMC8766667 DOI: 10.3389/fonc.2021.727027] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 12/03/2021] [Indexed: 12/12/2022] Open
Abstract
Although initial surgical excision cures 95% of patients, a minority of cutaneous squamous cell carcinomas (cSCCs) are judged to be unresectable, either locally advanced or with unresectable regional lymph nodes or distant metastases. These patients are offered systemic treatments. Response rate to chemotherapy is relatively low and not durable, as well as the results obtained with epidermal growth factor inhibitors (EGFRi). Like other cutaneous tumors, cSCCs have high immunogenicity, driven by the high mutational burden, the ultraviolet signature, and the overexpressed tumor antigens. Two checkpoint inhibitors, cemiplimab and pembrolizumab, achieved high response rate and survival with fewer toxicities than other available systemic agents. These promising results prompted to investigate new combination strategies of systemic therapy and surgery or radiotherapy. Subgroup analysis showed promising role of immunotherapy to facilitate surgery in locally advanced cSCC and, in a small group of patients, long-term survivals without resection. However, some cSCCs treated with immunotherapy develop either early or late resistance, so new drugs and new combinations are in a clinical study to overcome the mechanism underpinning these resistances. The present review focuses on the progress with immunotherapy to date and on new therapeutic strategies for cSCC.
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Affiliation(s)
- Andrea Alberti
- Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health University of Brescia, Azienda Socio Sanitaria Territoriale (ASST)-Spedali Civili, Brescia, Italy
| | - Paolo Bossi
- Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health University of Brescia, Azienda Socio Sanitaria Territoriale (ASST)-Spedali Civili, Brescia, Italy
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28
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Luo Y, Teng F, Fu H, Ding GS. Immunotherapy in liver transplantation for hepatocellular carcinoma: Pros and cons. World J Gastrointest Oncol 2022; 14:163-180. [PMID: 35116109 PMCID: PMC8790424 DOI: 10.4251/wjgo.v14.i1.163] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/30/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) has emerged as a curative strategy for hepatocellular carcinoma (HCC), but contributes to a higher predisposition to HCC recurrence in the immunosuppression context, especially for tumors beyond the Milan criteria. Although immunotherapy has dramatically improved survival for immunocompetent patients and has become the standard of care for a variety of tumors, including HCC, it is mainly used outside the scope of organ transplantation owing to potentially fatal allograft rejection. Nevertheless, accumulative evidence has expanded the therapeutic paradigms of immunotherapy for HCC, from downstaging or bridging management in the pretransplant setting to the salvage or adjuvant strategy in the posttransplant setting. Generally, immunotherapy mainly includes immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and vaccine therapy. ICIs, followed by ACT, have been most investigated in LT, with some promising results. Because of the complex tumor microenvironment and immunoreactivity when immunosuppressants are combined with immunotherapy, it is difficult to reach formulations for immunosuppressant adjustment and the optimal selection of immunotherapy as well as patients. In addition, the absence of effective biomarkers for identifying rejection and tumor response is still an unresolved barrier to successful clinical immunotherapy applications for LT. In this review, we comprehensively summarize the available evidence of immunotherapy used in LT that is specific to HCC. Moreover, we discuss clinically concerning issues regarding the concurrent goals of graft protection and antitumor response.
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Affiliation(s)
- Yi Luo
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Fei Teng
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Hong Fu
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Guo-Shan Ding
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
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29
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Dang N, Waer M, Sprangers B, Lin Y. Establishment of operational tolerance to sustain antitumor immunotherapy. J Heart Lung Transplant 2022; 41:568-577. [DOI: 10.1016/j.healun.2022.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 12/31/2021] [Accepted: 01/19/2022] [Indexed: 12/01/2022] Open
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30
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Zhang J, Miao X, Wu T, Jia J, Cheng X. Development and Validation of Ten-RNA Binding Protein Signature Predicts Overall Survival in Osteosarcoma. Front Mol Biosci 2021; 8:751842. [PMID: 34926575 PMCID: PMC8671810 DOI: 10.3389/fmolb.2021.751842] [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: 08/02/2021] [Accepted: 11/16/2021] [Indexed: 11/13/2022] Open
Abstract
Osteosarcoma is a malignant tumor that originates in the bones with the characteristics of high malignancy, predisposition to metastasis, and poor prognosis. RNA binding proteins (RBPs) are closely related to various tumors, but their relationship with osteosarcoma remains unclear. Based on GTEx and TARGET RNA sequencing data, we applied differential analysis to obtain RBP genes that are differentially expressed in osteosarcoma, and analyzed the functions of these RBPs. After applying univariate and LASSO Cox regression analysis, 10 key prognostic RBPs (TDRD6, TLR8, NXT2, EIF4E3, RPS27L, CPEB3, RBM34, TERT, RPS29, and ZC3HAV1) were screened, and an RBP prognostic risk assessment model for patients with osteosarcoma was established. The independent cohort GSE21257 was used for external verification, and the results showed that the signature has an excellent ability to predict prognosis. In addition, a nomogram that can be used for clinical evaluation was constructed. Finally, the expression levels of 10 prognostic RBPs in osteosarcoma cells and tissues were confirmed through experiments. Our study identified a ten-gene prognostic marker related to RBP, which is of great significance for adjusting the treatment strategy of patients with osteosarcoma and exploring prognostic markers.
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Affiliation(s)
- Jian Zhang
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Institute of Orthopedics of Jiangxi Province, Nanchang, China
| | - Xinxin Miao
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Institute of Orthopedics of Jiangxi Province, Nanchang, China
| | - Tianlong Wu
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Institute of Minimally Invasive Orthopedics, Nanchang University, Nanchang, China
| | - Jingyu Jia
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xigao Cheng
- Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Institute of Orthopedics of Jiangxi Province, Nanchang, China.,Institute of Minimally Invasive Orthopedics, Nanchang University, Nanchang, China
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31
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Majumdar S, Gupta S, Krishnamurthy S. Multifarious applications of bioactive glasses in soft tissue engineering. Biomater Sci 2021; 9:8111-8147. [PMID: 34766608 DOI: 10.1039/d1bm01104a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Tissue engineering (TE), a new paradigm in regenerative medicine, repairs and restores the diseased or damaged tissues and eliminates drawbacks associated with autografts and allografts. In this context, many biomaterials have been developed for regenerating tissues and are considered revolutionary in TE due to their flexibility, biocompatibility, and biodegradability. One such well-documented biomaterial is bioactive glasses (BGs), known for their osteoconductive and osteogenic potential and their abundant orthopedic and dental clinical applications. However, in the last few decades, the soft tissue regenerative potential of BGs has demonstrated great promise. Therefore, this review comprehensively covers the biological application of BGs in the repair and regeneration of tissues outside the skeleton system. BGs promote neovascularization, which is crucial to encourage host tissue integration with the implanted construct, making them suitable biomaterial scaffolds for TE. Moreover, they heal acute and chronic wounds and also have been reported to restore the injured superficial intestinal mucosa, aiding in gastroduodenal regeneration. In addition, BGs promote regeneration of the tissues with minimal renewal capacity like the heart and lungs. Besides, the peripheral nerve and musculoskeletal reparative properties of BGs are also reported. These results show promising soft tissue regenerative potential of BGs under preclinical settings without posing significant adverse effects. Albeit, there is limited bench-to-bedside clinical translation of elucidative research on BGs as they require rigorous pharmacological evaluations using standardized animal models for assessing biomolecular downstream pathways.
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Affiliation(s)
- Shreyasi Majumdar
- Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India.
| | - Smriti Gupta
- Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India.
| | - Sairam Krishnamurthy
- Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India.
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32
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de Jong E, Lammerts MUPA, Genders RE, Bouwes Bavinck JN. Update of advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 2021; 36 Suppl 1:6-10. [PMID: 34855246 PMCID: PMC9299882 DOI: 10.1111/jdv.17728] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 10/07/2021] [Indexed: 12/20/2022]
Abstract
The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing. A growing part of this patient group is formed by immunocompromised patients, for example organ-transplant recipients (OTR). Although over 90% of the cSCC show a relatively harmless clinical behaviour, there is also a chance of developing advanced cSCC and metastases. Locally advanced cSCC are defined as cSCC that have locally advanced progression and are no longer amenable to surgery or radiation therapy. Better understanding of the clinical behaviour of cSCC is essential to discriminate between low- and high-risk cSCC. Staging systems are important and have recently been improved. Genetic characterisation of SCC will likely become an important tool to help distinguish low and high-risk cSCC with an increased potential to metastasise in the near future. Available treatments for high-risk and advanced cSCC include surgery, radiotherapy, chemotherapy and targeted therapy with epidermal growth factor receptors inhibitors. Anti-PD-1 antibodies show promising results with response rates of up to 50% in both locally advanced and metastatic cSCC but, in its present form, is not suitable for OTR.
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Affiliation(s)
- E de Jong
- Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - M U P A Lammerts
- Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - R E Genders
- Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - J N Bouwes Bavinck
- Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands
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Neoadjuvant Therapy with Concurrent Docetaxel, Epirubicin, and Cyclophosphamide (TEC) in High-Risk HER2-Negative Breast Cancers. Adv Ther 2021; 38:5752-5762. [PMID: 34699004 DOI: 10.1007/s12325-021-01933-1] [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: 08/24/2021] [Accepted: 09/22/2021] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Concurrent anthracycline and taxane is an effective and efficient way to deliver neoadjuvant chemotherapy for HER2-negative breast cancers. Data on efficacy and tolerance to 6 cycles of concurrent docetaxel, epirubicin, and cyclophosphamide (TEC) is limited. METHOD All patients with HER2-negative breast cancers who received neoadjuvant TEC from January 2013 to December 2019 were reviewed. RESULTS A total of 71 patients [57 luminal B disease; 14 triple negative breast cancer (TNBC)] received neoadjuvant TEC with prophylactic granulocyte colony-stimulating factor (G-CSF). The pathological complete response (pCR) rate was 26.3% and 28.6% for luminal B and TNBC, respectively. With median follow-up of 48.9 months, 3 years disease-free survival was 85.9%, and 3 years overall survival was 89.6%. Non-hematological toxicities were common but the majority was grade 1 or 2. The most common grade 3 or 4 toxicity were hematological, including neutropenia (26.8%) and anemia (15.5%). There was no cardiotoxicity observed. Half of the patients had at least one dose reduction but all patients completed the planned 6 cycles and had breast surgery done. CONCLUSION Six cycles of TEC with prophylactic G-CSF is an effective and tolerable neoadjuvant regime for HER2-negative breast cancers. Hematological toxicities were the most common toxicities. Although many patients required dose reduction, all patients completed treatment and there was no observed cardiotoxicity.
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Vogel A, Sterneck M, Vondran F, Waidmann O, Klein I, Lindig U, Nadalin S, Settmacher U, Tacke F, Schlitt HJ, Wege H. [The use of immuno-oncologic therapy in hepatocellular carcinoma in the context of liver transplantation. An interdisciplinary benefit/risk assessment]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 60:184-191. [PMID: 34670296 DOI: 10.1055/a-1649-8643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Multiple systemic therapy options have been recently approved for the treatment of hepatocellular carcinoma (HCC). In particular, immuno-oncology combination therapies can now achieve impressive response rates and significantly prolonged survival with good tolerability. These immuno-oncology (IO)-based combinations are currently not only evaluated for the therapy of advanced HCC, but increasingly also in earlier stages in terms of peri-interventional therapy concepts and also for down-sizing to local therapies. In the context of liver transplantation (LTx), a particularly critical benefit/risk assessment must be made before the use of immunotherapeutics in the context of multimodal concepts, since the risk of a potentially lethal rejection can be significantly increased by immunotherapy. METHODS This review is based on a selective literature search performed between December 2020 and April 2021 in the PubMed and Cochrane Library databases. Guidelines, expert opinions, and recommendations from professional societies were given special consideration. RESULTS Nearly one in five LTx in Germany are performed due to HCCs. In this context, LTx is a curative therapy option not only for the underlying liver disease but also for the malignant tumor. Individual case reports indicate that IO therapy prior to LTx may increase the risk of rejection or liver failure after subsequent liver transplantation. Since 2015, immunotherapeutics have also been widely used for tumor therapy in patients after LTx. In small case series, rejection rates of 36%, associated with rejection-related mortality of 20% of treated patients, have been described. A similar incidence of rejection has also been described following the use of immunotherapeutics in patients after other organ transplantations. CONCLUSION In the context of organ transplantation, IO therapy carries the risk of graft rejection, which can lead to graft loss and also patient death. However, from today's point of view, IO-based therapy can be considered in the context of organ transplantation with a careful benefit/risk assessment.
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Affiliation(s)
- Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - Martina Sterneck
- I. Medizinische Klinik und Poliklinik, UKE Hamburg, Hamburg, Deutschland
| | - Florian Vondran
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - Oliver Waidmann
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Ingo Klein
- Klinik und Poliklinik für Allgemein-, Viszeral-, Transplantations-, Gefäß- und Kinderchirurgie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Udo Lindig
- Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Deutschland
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Hans Jürgen Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Henning Wege
- I. Medizinische Klinik und Poliklinik, UKE Hamburg, Hamburg, Deutschland.,Cancer Center Esslingen, Klinikum Esslingen, Esslingen, Deutschland
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Feng G, Li Q, Zhu H, Jiang Y, Yuan J, Fu Y, Deng Q. Safety and Efficacy of Anti-CD19-Chimeric Antigen Receptor T Cell Combined With Programmed Cell Death 1 Inhibitor Therapy in a Patient With Refractory Post-Transplant Lymphoproliferative Disease: Case Report and Literature Review. Front Oncol 2021; 11:726134. [PMID: 34604065 PMCID: PMC8481808 DOI: 10.3389/fonc.2021.726134] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Post-transplant lymphoproliferative disease (PTLD) often exhibits poor prognosis and high mortality, and there are no uniform guidelines for the treatment of this disease. Anti-CD19 chimeric antigen receptor (CAR) T cells show significant efficacy in treatment of relapse/refractory diffuse large B-cell lymphoma (DLBCL). Treatment using anti-CD19-CAR T-cell therapy in PTLD has been limited by immunosuppressants and has not been widely employed. In this study, a refractory post kidney transplant DLBCL patient with a high tumor burden was enrolled in a clinical trial of anti-CD19-CAR T-cell therapy. The tacrolimus dose was not decreased during combination chemotherapy, as the creatinine level of the patient increased. To improve the function of autologous T cells, combination therapy with anti-CD19-CAR T cells and programmed cell death 1 (PD-1) inhibitors was selected. After treatment with the combination therapy, the patient was diagnosed with grade 1 cytokine release syndrome and grade 3 immune effector cell-associated neurotoxicity syndrome. The amplification peak of anti-CD19-CAR T cells reached 9.01% on day 7. With PD-1 inhibitor maintenance therapy, his disease was maintained in partial remission for 18 weeks. However, his tumor suddenly increased in size, and he discontinued the treatment, including radiation therapy. The anti-CD19-CAR T cell and PD-1 inhibitors have a combined effect on PTLD, and this combination therapy needs to be further explored.
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Affiliation(s)
- Gang Feng
- Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Qing Li
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Haibo Zhu
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Yanyu Jiang
- Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Jijun Yuan
- Shanghai Genbase Biotechnology Co. Ltd., Shanghai, China
| | - Yingxin Fu
- Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Qi Deng
- Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
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Carlino MS, Larkin J, Long GV. Immune checkpoint inhibitors in melanoma. Lancet 2021; 398:1002-1014. [PMID: 34509219 DOI: 10.1016/s0140-6736(21)01206-x] [Citation(s) in RCA: 674] [Impact Index Per Article: 168.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 03/30/2021] [Accepted: 05/19/2021] [Indexed: 12/14/2022]
Abstract
Immune checkpoint inhibitors target the dysfunctional immune system, to induce cancer-cell killing by CD8-positive T cells. Immune checkpoint inhibitors, specifically anti-CTLA4 and anti-PD-1 antibodies, have revolutionised the management of many cancers, particularly advanced melanoma, for which tumour regression and long-term durable cancer control is possible in nearly 50% of patients, compared with less than 10% historically. Despite the absence of adequately powered trial data, combined anti-CTLA4 and anti-PD-1 checkpoint inhibition has the highest 5-year overall survival rate of all therapies in advanced melanoma, and has high activity in melanoma brain metastases. A phase 3 study has shown the addition of an anti-LAG3 antibody to nivolumab improves progression-free survival, but its effect on overall survival and how this combination compares to combined anti-CTLA4 and anti-PD-1 checkpoint inhibition is unknown. At present, there are no highly sensitive and specific biomarkers of response to immune checkpoint inhibitors, and clinical factors, such as volume and sites of disease, serum lactate dehydrogenase, and BRAF mutation status, are used to select initial therapy for patients with advanced melanoma. Immune checkpoint inhibitors can induce autoimmune toxicities by virtue of their mechanism of action. These toxicities, termed immune-related adverse events, occur most frequently with combined anti-CTLA4 and anti-PD-1 checkpoint inhibition; can have a variety of presentations; can affect any organ system (most often the skin, colon, endocrine system, and liver); and appear to mimic classic autoimmune diseases. Immune-related adverse events require prompt recognition and management, which may be different from the autoimmune disease it mimics. Immune checkpoint inhibitors appear to be safe for use in patients with HIV, viral hepatitis, and patients with mild-to-moderate pre-existing autoimmune diseases. Patients with organ transplants can respond to immune checkpoint inhibitors but have a high chance of transplant loss. PD-1 inhibitors are now an established standard of care as adjuvant therapy in high-risk resected stage III or IV melanoma. Neoadjuvant checkpoint inhibition for resectable stage III melanoma, which is currently limited to clinical trials, is emerging as a highly effective therapy.
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Affiliation(s)
- Matteo S Carlino
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology Blacktown and Westmead Hospitals, Sydney, NSW, Australia
| | - James Larkin
- The Royal Marsden NHS Foundation Trust, London, UK
| | - Georgina V Long
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Royal North Shore and Mater Hospitals, North Sydney, Sydney, NSW, Australia.
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Central nervous system infections after solid organ transplantation. Curr Opin Infect Dis 2021; 34:207-216. [PMID: 33741794 DOI: 10.1097/qco.0000000000000722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE OF REVIEW Significant advances to our understanding of several neuroinfectious complications after a solid organ transplant (SOT) have occurred in the last few years. Here, we review the central nervous system (CNS) infections that are relevant to SOT via a syndromic approach with a particular emphasis on recent updates in the field. RECENT FINDINGS A few key studies have advanced our understanding of the epidemiology and clinical characteristics of several CNS infections in SOT recipients. Risk factors for poor prognosis and protective effects of standard posttransplant prophylactic strategies have been better elucidated. Newer diagnostic modalities which have broad clinical applications like metagenomic next-generation sequencing, as well as those that help us better understand esoteric concepts of disease pathogenesis have been studied. Finally, several studies have provided newer insights into the treatment of these diseases. SUMMARY Recent findings reflect the steady progress in our understanding of CNS infections post SOT. They provide several avenues for improvement in the prevention, early recognition, and therapeutic outcomes of these diseases.
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Piñero F, da Fonseca LG. Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups? World J Gastroenterol 2021; 27:3429-3439. [PMID: 34239261 PMCID: PMC8240059 DOI: 10.3748/wjg.v27.i24.3429] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/06/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Although hepatocellular carcinoma is considered a highly lethal malignancy, recent therapeutic advances have been achieved during the last 10 years. This scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma, almost reaching 20-26 mo of overall survival after first-second line sequential treatment. The advent of the combination of atezolizumab with bevacizumab showed, for the first time, superiority over sorafenib with improvement in overall survival. However, first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure, decompensated cirrhosis or other underlying medical conditions. As a result, the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups, such as patients with unpreserved liver function, other comorbid conditions, a history of solid-organ transplantation, autoimmune disorders and those with a high risk of bleeding. The present text aims at discussing treatment strategies in these subgroups.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires B1629HJ, Argentina
| | - Leonardo Gomes da Fonseca
- Clinical Oncology, Insituto do Cancer do Estado de São Paulo, University of São Paulo, São Paulo 05403-000, Brazil
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Nguyen LS, Ortuno S, Lebrun-Vignes B, Johnson DB, Moslehi JJ, Hertig A, Salem JE. Transplant rejections associated with immune checkpoint inhibitors: A pharmacovigilance study and systematic literature review. Eur J Cancer 2021; 148:36-47. [DOI: 10.1016/j.ejca.2021.01.038] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 12/25/2020] [Accepted: 01/29/2021] [Indexed: 12/20/2022]
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Ishikawa G, Sugiyama T, Ito T, Otsuka A, Miyake H. Renal allograft rejection after treatment with nivolumab in patients with metastatic renal cell carcinoma. Int Cancer Conf J 2021; 10:116-118. [PMID: 33786286 DOI: 10.1007/s13691-020-00458-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 11/14/2020] [Indexed: 11/24/2022] Open
Abstract
In recent years, immune checkpoint inhibitors (ICIs), such as nivolumab, pembrolizumab and ipilimumab, have been introduced into routine clinical practice for treating patients with several types of advanced cancer, including renal cell carcinoma (RCC). However, activation of the immune system against cancer cells by the use of ICIs could result in the induction of allograft rejection in organ transplant patients, and to date, the safety of treatment for organ transplant patients with ICIs has not been well-investigated. Here, we report a case of renal allograft rejection in a kidney transplant recipient with metastatic RCC (mRCC) after the administration of nivolumab. Four weeks after initiating treatment with nivolumab, the renal function, in this case, was markedly impaired, and pathological findings of renal biopsy specimens showed acute rejection characterized by marked infiltration of inflammatory cells. Steroid pulse therapy was performed in this case, and despite the lack of improvement in the renal function, his graft was salvaged. Collectively, these findings suggest that it is necessary to pay special attention to the potential for allograft rejection when introducing ICIs for solid organ transplant recipients.
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Affiliation(s)
- Gaku Ishikawa
- Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takayuki Sugiyama
- Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Toshiki Ito
- Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Atsushi Otsuka
- Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hideaki Miyake
- Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Utility of Serial Donor-derived Cell-free DNA Measurements for Detecting Allograft Rejection in a Kidney Transplant Recipient After PD-1 Checkpoint Inhibitor Administration. Transplant Direct 2021; 7:e656. [PMID: 33490381 PMCID: PMC7817285 DOI: 10.1097/txd.0000000000001113] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/03/2020] [Accepted: 11/04/2020] [Indexed: 01/09/2023] Open
Abstract
Background. Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker of rejection that originates from allograft cells undergoing injury. Plasma levels <1% in kidney transplant recipients have a high negative predictive value for active allograft rejection. The utility of this biomarker in kidney transplant recipients receiving immune checkpoint inhibitor therapy is unknown. Methods. We describe a case in which serial dd-cfDNA monitoring facilitated the use of immune checkpoint inhibitor therapy, which is known to be associated with high rates of rejection, in a kidney transplant recipient with metastatic cancer. Results. A 72-y-old man with end-stage kidney disease secondary to autosomal dominant polycystic kidney disease underwent living unrelated kidney transplant in December 2010. His immunosuppression regimen included tacrolimus, mycophenolate, and prednisone. In July 2017, he presented with metastatic cutaneous squamous cell carcinoma. After his disease progressed through radiation therapy and cetuximab, he received pembrolizumab (antiprogrammed cell death protein 1). His dd-cfDNA level was undetectable at baseline, then increased during treatment but remained <1%. This trend, despite fluctuations in serum creatinine levels during therapy, allowed for continuation of pembrolizumab and successful treatment of his metastatic cancer without clinically evident allograft rejection. After discontinuation of pembrolizumab, dd-cfDNA levels fell below the level of detection. Genetic analysis of the cutaneous squamous cell carcinoma demonstrated a genetic profile distinct from the dd-cfDNA, indicating that tumor lysis did not impact increases in dd-cfDNA. Conclusions. Serial dd-cfDNA measurements may provide a useful, noninvasive biomarker for detecting allograft injury that may facilitate the use of immunomodulatory therapies in organ transplant recipients with cancer.
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Delyon J, Zuber J, Dorent R, Poujol-Robert A, Peraldi MN, Anglicheau D, Lebbe C. Immune Checkpoint Inhibitors in Transplantation-A Case Series and Comprehensive Review of Current Knowledge. Transplantation 2021; 105:67-78. [PMID: 32355121 DOI: 10.1097/tp.0000000000003292] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Cancer is a leading cause of morbidity and deaths in solid organ transplant recipients. In immunocompetent patients, cancer prognosis has been dramatically improved with the development of immune checkpoint inhibitors (ICI), as programmed cell death protein 1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen 4 inhibitors, that increase antitumor immune responses. ICI has been developed outside of the scope of transplantation because of the theoretical risk of graft rejection, which has later been confirmed by the publication of several cases and small series. The use of ICI became unavoidable for treating advanced cancers including in organ transplant patients, but their management in this setting remains highly challenging, as to date no strategy to adapt the immunosuppression and to prevent graft rejection has been defined. In this article, we report a monocentric series of 5 solid organ transplant recipients treated with ICI and provide a comprehensive review of current knowledge of ICI management in the setting of solid organ transplantation. Strategies warranted to increase knowledge through collecting more exhaustive data are also discussed.
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Affiliation(s)
- Julie Delyon
- Department of Dermatology, AP-HP Hôpital Saint Louis, Université de Paris, INSERM U976, Team 1, HIPI, Paris, France
| | - Julien Zuber
- Department of Nephrology and Kidney Transplantation, University Hospital Center (CHU) Necker, Université de Paris, Paris, France
| | - Richard Dorent
- Department of Cardiac Surgery, AP-HP, Bichat-Claude Bernard University Hospital, Paris, France
| | - Armelle Poujol-Robert
- Department of Hepatology, AP-HP, Hôpital Saint-Antoine, UPMC University, Paris, France
| | - Marie-Noelle Peraldi
- Department of Nephrology, AP-HP Hôpital Saint Louis, Université de Paris, Paris, France
| | - Dany Anglicheau
- Department of Nephrology and Kidney Transplantation, University Hospital Center (CHU) Necker, Université de Paris, Paris, France
| | - Celeste Lebbe
- Department of Dermatology, AP-HP Hôpital Saint Louis, Université de Paris, INSERM U976, Team 1, HIPI, Paris, France
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Piñero F, Thompson M, Marín JI, Silva M. Lenvatinib as first-line therapy for recurrent hepatocellular carcinoma after liver transplantation: Is the current evidence applicable to these patients? World J Transplant 2020; 10:297-306. [PMID: 33312891 PMCID: PMC7708877 DOI: 10.5500/wjt.v10.i11.297] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/09/2020] [Accepted: 09/22/2020] [Indexed: 02/05/2023] Open
Abstract
Liver transplantation (LT) is one of the leading curative therapies for hepatocellular carcinoma (HCC). Despite recent optimization of transplant selection criteria, including alpha-feto protein, HCC recurrence after LT is still the leading cause of death in these patients. During the last decades, effective systemic treatments for HCC, including tyrosine kinase inhibitors and immunotherapy, have been approved. We describe the clinical scenario of a patient with recurrence of HCC five years after LT, who received lenvatinib as first-line systemic therapy to introduce systemic treatment options in this clinical setting. In this opinion review, we detail first and second-line systemic treatment options, focusing on those feasible for patients with recurrent HCC after LT. Several trials have evaluated new drugs to treat HCC patients in first and second-line therapy, but patients with recurrent HCC after LT have been excluded from these trials. Consequently, most of the evidence comes from observational retrospective studies. Whether tyrosine kinase inhibitors will remain the primary therapeutic approach in these patients, due to a relative contraindication for immunotherapy, may be clarified in the near future.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires B1629HJ, Argentina
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires B1629HJ, Argentina
| | - Marcos Thompson
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
| | - Juan Ignacio Marín
- Hepatology and Liver Transplantation Unit, Hospital Pablo Tobón Uribe, Medellín 240, Colombia
| | - Marcelo Silva
- Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires B1629HJ, Argentina
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Padala SA, Patel SK, Vakiti A, Patel N, Gani I, Kapoor R, Muhammad S. Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy. J Oncol Pharm Pract 2020; 27:470-476. [PMID: 32580640 DOI: 10.1177/1078155220934160] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. CASE REPORT We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. DISCUSSION As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.
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Affiliation(s)
- Sandeep A Padala
- Department of Medicine, Nephrology, Augusta University, Medical College of Georgia, Augusta, USA
| | - Shivam K Patel
- Department of Medicine, Medical College of Georgia, Augusta, USA
| | - Anusha Vakiti
- Department of Medicine, Hematology-Oncology, Augusta University Medical Center, Medical College of Georgia, Augusta, USA
| | - Nikhil Patel
- Department of Pathology, Augusta University Medical Center, Medical College of Georgia, Augusta, USA
| | - Imran Gani
- Department of Medicine, Nephrology, Augusta University Medical Center, Medical College of Georgia, Augusta, USA
| | - Rajan Kapoor
- Department of Medicine, Nephrology, Augusta University Medical Center, Medical College of Georgia, Augusta, USA
| | - Saeed Muhammad
- Department of Surgery, Transplant Nephrology, Augusta University Medical Center, Medical College of Georgia, Augusta, USA
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Willenbrink TJ, Jambusaria-Pahlajani A, Arron S, Seckin D, Harwood CA, Proby CM. Treatment approaches in immunosuppressed patients with advanced cutaneous squamous cell carcinoma. J Eur Acad Dermatol Venereol 2020; 33 Suppl 8:57-60. [PMID: 31833603 DOI: 10.1111/jdv.15843] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 07/29/2019] [Indexed: 12/17/2022]
Abstract
Immunosuppression, both iatrogenic and disease-related, is associated with a greatly increased incidence of cutaneous SCC (cSCC) and with aggressive cSCC and worse disease outcomes. Consequently, rapid access to skin cancer services and prudent surgical choices, such as circumferential margin assessment, is essential when treating advanced cSCC in an immunosuppressed patient. For high-risk cancers and control of cSCC multiplicity, additional strategies should be actively considered within the multidisciplinary clinical care team. These include minimization or revision of immunosuppressive medications, systemic chemoprevention (including retinoids, nicotinamide, capecitabine) and adjuvant therapies such as radiotherapy. Unfortunately, there is a relative paucity of good evidence for many of these treatments in the immunosuppressed. Systemic treatments for metastatic cSCC are often contraindicated in organ transplant recipients, notably checkpoint inhibitor immunotherapy. There are also toxicity concerns with some conventional chemotherapies and EGFR inhibitors. Until recently, clinical trials have largely excluded immunosuppressed individuals. Development of more effective treatment for advanced cSCC in this high-risk group and prospective clinical trials are now research priorities.
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Affiliation(s)
- T J Willenbrink
- Division of Dermatology, Department of Internal Medicine, The University of Texas at Austin-Dell Medical School, Austin, TX, USA
| | - A Jambusaria-Pahlajani
- Division of Dermatology, Department of Internal Medicine, The University of Texas at Austin-Dell Medical School, Austin, TX, USA
| | - S Arron
- Department of Dermatology, University of California, San Francisco, CA, USA
| | - D Seckin
- Department of Dermatology, Faculty of Medicine, Baskent University, Ankara, Turkey
| | - C A Harwood
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - C M Proby
- Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital, Dundee, UK
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Hanna DL, Law SJ, Merrick SA, Heptinstall L, Bass P, Dupont P, Sheri A. The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma. Melanoma Res 2020; 30:321-324. [PMID: 31764435 DOI: 10.1097/cmr.0000000000000651] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
We report a case in which a renal transplant recipient with metastatic melanoma had an excellent response to treatment with second line programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab. Acute cellular allograft rejection on initiation of PD-1 inhibitor was successfully reversed with methylprednisolone. By converting the patient to sirolimus and giving predose prednisolone, pembrolizumab was continued with stable renal function and an excellent oncological response. This case supports the efficacy of PD-1 inhibitors in patients who are chronically immunosuppressed, and suggests an approach to maintain transplant function.
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Affiliation(s)
- Daire L Hanna
- Royal Free Hospital, Pond Street, Hampstead, London, UK
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Fisher J, Zeitouni N, Fan W, Samie FH. Immune checkpoint inhibitor therapy in solid organ transplant recipients: A patient-centered systematic review. J Am Acad Dermatol 2020; 82:1490-1500. [DOI: 10.1016/j.jaad.2019.07.005] [Citation(s) in RCA: 114] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 06/12/2019] [Accepted: 07/03/2019] [Indexed: 02/06/2023]
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Crepeau RL, Ford ML. Programmed T cell differentiation: Implications for transplantation. Cell Immunol 2020; 351:104099. [PMID: 32247511 DOI: 10.1016/j.cellimm.2020.104099] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/27/2020] [Accepted: 03/27/2020] [Indexed: 12/27/2022]
Abstract
While T cells play a critical role in protective immunity against infection, they are also responsible for graft rejection in the setting of transplantation. T cell differentiation is regulated by both intrinsic transcriptional pathways as well as extrinsic factors such as antigen encounter and the cytokine milieu. Herein, we review recent discoveries in the transcriptional regulation of T cell differentiation and their impact on the field of transplantation. Recent studies uncovering context-dependent differentiation programs that differ in the setting of infection or transplantation will also be discussed. Understanding the key transcriptional pathways that underlie T cell responses in transplantation has important clinical implications, including development of novel therapeutic agents to mitigate graft rejection.
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Affiliation(s)
- Rebecca L Crepeau
- Emory Transplant Center, Department of Surgery, Emory University, 101 Woodruff Circle, Suite 5208, Atlanta, GA 30322, United States
| | - Mandy L Ford
- Emory Transplant Center, Department of Surgery, Emory University, 101 Woodruff Circle, Suite 5208, Atlanta, GA 30322, United States.
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49
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Antonuzzo A, Calabrò F, Quaglino P, Roila F, Sebastiani GD, Spina F, Pasqualetti G, Cortinovis D, Tagliaferri E, Peri A, Presotto EM, Egidi MF, Giacomelli L, Farroni F, Di Maio M, De Luca E, Danova M, Scottè F, Jordan K, Bossi P. Immunotherapy in Underrepresented Populations of Patients with Cancer: Do We Have Enough Evidence at Present? A Focus on Patients with Major Viral Infections and Autoimmune Disorders. Oncologist 2020; 25:e946-e954. [PMID: 32181960 DOI: 10.1634/theoncologist.2020-0035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 01/21/2020] [Indexed: 12/12/2022] Open
Abstract
The safety and activity of immune checkpoint inhibitors have been characterized in interventional and observational studies. However, only small studies have specifically investigated these agents in patients who are excluded or underrepresented in clinical trials, frequently referred to as "special populations" or "underrepresented populations." These include older adults, those with dysregulated immune activation, patients with a compromised immune function, and those carrying major viral infections, lymphoproliferative diseases, and major organ dysfunctions. Therefore, there remains substantial uncertainty regarding the use of immune checkpoint inhibitors in these specific settings. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project, with the contribution of oncologists and other specialists, to retrieve the existing evidence on the use of immunotherapy in patients with solid and hematological cancers with the final aim to provide an expert guidance. The results of this effort are presented in this article, which is focused on patients with major viral infections or those with immune dysregulation/autoimmune diseases, and could be useful to guide decisions in clinical practice and to design prospective clinical trials focusing on the use of immunotherapy in these populations. IMPLICATIONS FOR PRACTICE: Substantial uncertainty remains regarding the use of immune checkpoint inhibitors in "underrepresented" patients, such as older adults, those with dysregulated immune activation, and patients with a compromised immune function, major viral infections, lymphoproliferative diseases or major organ dysfunctions. The Network of Italian Supportive Care in Oncology has carried out a multidisciplinary project to retrieve the existing evidence on the use of immunotherapy in underrepresented patients with cancer in order provide an expert guidance. The results of this effort, with a focus on patients with major viral infections or those with immune dysregulation/autoimmune diseases, are presented in this article and could be useful to guide decisions both in clinical practice and to design clinical trials.
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Affiliation(s)
- Andrea Antonuzzo
- UO Oncologia 1 SSN Polo Oncologico, Ambulatorio Terapie di Supporto, Pisa, Italy
| | | | - Pietro Quaglino
- Dermatologic Clinic, Department of Medical Sciences, Turin, Italy
| | - Fausto Roila
- Department of Medical Oncology, Azienda Ospedaliera, Universitaria Perugia, Italy
| | - Gian Domenico Sebastiani
- Unità Operativa Complessa di Reumatologia, Ospedale di Alta Specializzazione "San Camillo,", Rome, Italy
| | - Francesco Spina
- Division of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Tumori, Milan, Italy
| | | | | | | | - Alessandro Peri
- Sodium Unit, Endocrinology, Department of Experimental and Clinical Biomedical Sciences, Mario Serio, University of Florence, Careggi Hospital, Florence, Italy
| | - Elena Margherita Presotto
- Sodium Unit, Endocrinology, Department of Experimental and Clinical Biomedical Sciences, Mario Serio, University of Florence, Careggi Hospital, Florence, Italy
| | | | - Luca Giacomelli
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
- Polistudium SRL, Milan, Italy
| | - Ferruccio Farroni
- Gastroenterology Department, Foligno Hospital, Unità Sanitaria Locale Umbria 2, Foligno, Italy
| | - Massimo Di Maio
- Department of Oncology, University of Turin, Turin, Italy
- Division of Medical Oncology, Azienda Ospedaliero Ordine Mauriziano Hospital, Turin, Italy
| | - Emmanuele De Luca
- Department of Oncology, University of Turin, Turin, Italy
- Division of Medical Oncology, Azienda Ospedaliero Ordine Mauriziano Hospital, Turin, Italy
| | - Marco Danova
- Department of Internal Medicine and Medical Oncology, Vigevano Civic Hospital, Azienda Socio Sanitaria Territoriale (ASST) of Pavia, Pavia, Italy
| | - Florian Scottè
- Medical Oncology and Supportive Care Department, Hôpital Foch, Suresnes, France
| | - Karin Jordan
- Leitende Oberärztin, Klinik für Hämatologie, Onkologie und Rheumatologie, Innere Medizin V, Universitätsklinikum Heidelberg, Heidelberg, Germany
| | - Paolo Bossi
- Medical Oncology, University of Brescia, ASST-Spedali Civili, Brescia, Italy
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50
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Nordness MF, Hamel S, Godfrey CM, Shi C, Johnson DB, Goff LW, O'Dell H, Perri RE, Alexopoulos SP. Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient? Am J Transplant 2020; 20:879-883. [PMID: 31550417 PMCID: PMC10176099 DOI: 10.1111/ajt.15617] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 08/23/2019] [Accepted: 09/03/2019] [Indexed: 01/25/2023]
Abstract
Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.
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Affiliation(s)
- Mina F Nordness
- Section of Surgical Sciences, Department of Surgery, Division of Hepatobiliary Surgery & Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Stephanie Hamel
- Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Caroline M Godfrey
- Section of Surgical Sciences, Department of Surgery, Division of Hepatobiliary Surgery & Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Chanjuan Shi
- Department of Pathology, Vanderbilt University Medical Center, Microbiology, Microbiology, Nashville, Tennessee
| | - Douglas B Johnson
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Laura W Goff
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Heather O'Dell
- Section of Surgical Sciences, Department of Surgery, Division of Hepatobiliary Surgery & Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Roman E Perri
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Sophoclis P Alexopoulos
- Section of Surgical Sciences, Department of Surgery, Division of Hepatobiliary Surgery & Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
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