Abstract
Multiple myeloma (MM) remains an incurable plasma cells malignancy because of its complex genetic heterogeneity and high relapse rate post immunotherapy. The encouraging results of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) immunotherapy clinical trials have shed light on curing MM in recent years. However, many therapeutic side effects limit the promotion and clinical use of this novel effective approach such as cytokine release syndrome, antigen escape, and neurotoxicity. We should make every effort to do further study about this immunotherapy to make it safer and effective. This review focusing on this topic clarifies the following contents: present status of MM treatment, effectiveness of CAR-T cells, features of BCMA, preclinical and clinical trials of BCMA CAR-T cells therapy, and existing problems and strategies. Hoping to provide a reference for the subsequent correlative clinical and research.
Highlights
Multiple myeloma remains a highly incurable fatal hematopoietic malignancy and potentially curative and safer novel treatments are required
By systematically retrieving the research report and literature on this content and analyzing comprehensively, we find that the B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells immunotherapy shows great promise but still have many problems need to be resolved [1,2,3]
MM usually goes through the following stages: premalignant precursor condition, monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), active MM, and end-stage plasma cell leukemia (PCL)
Summary
Multiple myeloma remains a highly incurable fatal hematopoietic malignancy and potentially curative and safer novel treatments are required. The first-in-human clinical trial investigating the efficacy and safety of the 2nd–generation anti-BCMA-CAR with CD3/CD28 signaling domains was conducted by Kochenderfer et al in 2016 This group had reported their work on a novel CAR targeting BCMA in multiple myeloma and demonstrated the efficacy against myeloma cells in preclinical models about 3 years ago [44]. The higher level group had more serious toxicity such as cytokine release syndrome (CRS) with symptoms including fever, hypotension, dyspnea, and prolonged cytopenia [50] This clinical trial provides the first proof of the novel approach and clearly reveals the antimyeloma activity power of the anti-BCMA CAR-T cells. The relapsed/ refractory MM patients included in this trial needed adequate renal, hepatic, cardiac, and pulmonary function but no specific BCMA expression level They were designed to receive splitdose infusions of BCMA CAR-T cells (10% on day 0, 30% on day 1, and 60% on day 2). One of the patients who received 2 × 108 CAR-T cells had VGPR progressed at 5 months
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