Review
Pharmacology & Pharmacy
Taewoong Choi, Yubin Kang
Summary: Although treatment outcomes for multiple myeloma patients have greatly improved in the past two decades, the disease remains incurable. New immunotherapies, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, have emerged to treat multiple myeloma. This article provides a comprehensive review of the clinical efficacy, safety, and potential resistance mechanisms of current myeloma CAR-T therapies, with a focus on B Cell Maturation Antigen (BCMA) as the most successful target. The article also discusses novel strategies to enhance the effectiveness of myeloma CAR-T therapy.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
Jieyun Xia, Hujun Li, Zhiling Yan, Dian Zhou, Ying Wang, Yuekun Qi, Jiang Cao, Depeng Li, Hai Cheng, Wei Sang, Feng Zhu, Haiying Sun, Wei Chen, Kunming Qi, Dongmei Yan, Tingting Qiu, Jianlin Qiao, Ruosi Yao, Yang Liu, Xue Wang, Yanlei Zhang, Shuixiu Peng, Chih-Hua Huang, Junnian Zheng, Zhenyu Li, Alex H. H. Chang, Kailin Xu
Summary: This study evaluated the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma (MM). The results showed that anti-GPRC5D CAR T-cell therapy had good clinical efficacy and manageable safety in patients, especially for those who were previously unresponsive to anti-BCMA CAR T-cell therapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Jinrong Yang, Weilin Zhou, Dan Li, Ting Niu, Wei Wang
Summary: This article summarizes the application and research progress of BCMA-targeting CAR T cell therapy in the treatment of multiple myeloma, as well as measures to improve efficacy and safety.
Article
Immunology
Qiqi Zhang, Cheng Zu, Ruirui Jing, Youqin Feng, Yanlei Zhang, Mingming Zhang, Yuqi Lv, Jiazhen Cui, Linhui Zhou, Ye Meng, Linqin Wang, Zenan Cen, Alex H. H. Chang, Yongxian Hu, He Huang
Summary: This study aimed to investigate the incidence, clinical characteristics, and prognosis of CAR-T cell-related tumor lysis syndrome (TLS) in patients with refractory or relapsed multiple myeloma (r/r MM) treated with BCMA-targeted CAR-T therapy. The results showed that 17.1% of patients developed TLS after CAR-T cell therapy. TLS development had a negative impact on clinical response and prognosis, highlighting the importance of close monitoring for TLS during CAR-T cell therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Dongpeng Jiang, Haiwen Huang, Huimin Qin, Koukou Tang, Xiangru Shi, Tingting Zhu, Yuqing Gao, Ying Zhang, Xiaopeng Tian, Jianhong Fu, Weiwei Qu, Weilan Cai, Yang Xu, Depei Wu, Jianhong Chu
Summary: BCMA-targeting CAR-T therapy has shown promising responses in MM, but alternative targets are needed for BCMA-deficient tumors and BCMA antigen-loss relapse. This study reveals that FcRH5 is expressed on MM cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells exhibit antigen-specific activation, cytokine secretion, and cytotoxicity against MM cells, and show robust tumoricidal efficacy in mouse models. FcRH5/BCMA-bispecific CAR-T cells demonstrate improved efficacy compared to mono-specific CAR-T cells.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Xi Zhang, Yu Yang Ng, Zhicheng Du, Zhendong Li, Can Chen, Lin Xiao, Wee Joo Chng, Shu Wang
Summary: Modification of Vγ9Vδ2 T cells with a BCMA-specific CAR enhances their cytotoxicity against multiple myeloma cells, leading to a significant reduction in tumor burden and prolonged survival in a mouse model.
Editorial Material
Medicine, General & Internal
Sham Mailankody, Ola Landgren
Summary: BCMA has been recognized as a prognostic marker in multiple myeloma for over two decades, and is now a major target for various treatments including CAR T cells, antibody drug conjugates, and bispecific antibodies. The rapid translation from preclinical studies to FDA-approved treatments demonstrates significant success in the field.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Hematology
Arjun Lakshman, Shaji K. Kumar
Summary: For multiple myeloma patients refractory to current therapies, CAR T-lymphocytes, bsAbs, and ADCs show potential with ide cel and belamaf approved in the relapsed/refractory setting. bsAbs demonstrate promising quick and deep responses in clinical trials.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Review
Oncology
Rujul H. Parikh, Sagar Lonial
Summary: Multiple myeloma is a difficult-to-cure hematologic malignancy. Chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in relapsed, refractory multiple myeloma patients, but durable responses are still a challenge. This comprehensive review discusses the development of CAR T-cell therapies, clinical trial outcomes, toxicities and limitations, and strategies to overcome therapeutic challenges, aiming for a cure for multiple myeloma.
CA-A CANCER JOURNAL FOR CLINICIANS
(2023)
Article
Oncology
Shlomit Kfir-Erenfeld, Nathalie Asherie, Sigal Grisariu, Batia Avni, Eran Zimran, Miri Assayag, Tatyana Dubnikov Sharon, Marjorie Pick, Eyal Lebel, Adir Shaulov, Yael C. Cohen, Irit Avivi, Cyrille J. Cohen, Polina Stepensky, Moshe E. Gatt
Summary: BCMA-CART cells provide a safe and highly efficacious treatment option for advanced, RR AL patients.
CLINICAL CANCER RESEARCH
(2022)
Review
Medicine, General & Internal
Agnieszka Stelmach-Goldys, Monika Zaborek-Lyczba, Jakub Lyczba, Bartosz Garus, Marcin Pasiarski, Paulina Mertowska, Paulina Malkowska, Rafal Hrynkiewicz, Paulina Niedzwiedzka-Rystwej, Ewelina Grywalska
Summary: AL amyloidosis is a systemic disease characterized by the deposition of protein fibers formed from light chains produced by neoplastic clone of plasmocytes. Late diagnosis leads to high mortality rate, and the complex clinical picture and slow progression of the disease contribute to the delayed diagnosis. Early diagnosis and correct identification of the type of amyloidosis are crucial for treatment planning and effectiveness.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Yu Yang Ng, Zhicheng Du, Xi Zhang, Wee Joo Chng, Shu Wang
Summary: The study demonstrates that the co-expression of CXCR4 and anti-BCMA CAR on NK cells is an effective way to control MM progression by enhancing NK cell infiltration into the bone marrow and reducing tumor burden, leading to prolonged survival of patients.
CANCER GENE THERAPY
(2022)
Review
Medicine, Research & Experimental
Shirin Teymouri Nobari, Jafar Nouri Nojadeh, Mehdi Talebi
Summary: BCMA is a transmembrane glycoprotein highly expressed on plasma cells of MM patients and the normal population. It is used as a biomarker for MM. Proteins related to BCMA play a crucial role in plasma cell survival and MM progression. Various antibody and CAR-T cell therapies have been used for anti-MM treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Frank Cichocki, Ryan Bjordahl, Jodie P. Goodridge, Sajid Mahmood, Svetlana Gaidarova, Ramzey Abujarour, Zachary B. Davis, Aimee Merino, Katie Tuininga, Hongbo Wang, Akhilesh Kumar, Brian Groff, Alec Witty, Greg Bonello, Janel Huffman, Thomas Dailey, Tom T. Lee, Karl-Johan Malmberg, Bruce Walcheck, Uta Hoepken, Armin Rehm, Bahram Valamehr, Jeffrey S. Miller
Summary: The study presents quadruple gene-engineered induced pluripotent stem cell (iPSC)-derived NK cells as a potential therapy for multiple myeloma, demonstrating durable antitumor activity independent of exogenous cytokine support.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Xue Wang, Lina Zhao, Jing Wang, Yue Yao, Jiaojiao Wang, Shengwei Ji, Tian Hua, Shiyuan Wang, Hai Cheng, Ming Shi, Zhenyu Li, Lingyu Zeng, Junnian Zheng, Kailin Xu, Jiang Cao
Summary: This study confirmed the effectiveness of chimeric antigen receptor T (CAR-T) cell therapy in treating multiple myeloma. However, the severity of cytokine release syndrome (CRS) can impact patient survival. Analysis of 54 patients revealed a correlation between CRS severity and progression-free survival (PFS) and overall survival (OS), as well as an independent association between bone marrow tumor burden and CRS.
FRONTIERS IN IMMUNOLOGY
(2022)