Abstract
The emergence of various novel therapies over the last decade has changed the therapeutic landscape for multiple myeloma. While the clinical outcomes have improved significantly, the disease remains incurable, typically in patients with relapsed and refractory disease. Chimeric antigen receptor (CAR) T-cell therapies have achieved remarkable clinical success in B-cell malignancies. This scope of research has more recently been extended to the field of myeloma. While B-cell maturation antigen (BCMA) is currently the most well-studied CAR T antigen target in this disease, many other antigens are also undergoing intensive investigations. Some studies have shown encouraging results, whereas some others have demonstrated unfavorable results due to reasons such as toxicity and lack of clinical efficacy. Herein, we provide an overview of CAR T-cell therapies in myeloma, highlighted what has been achieved over the past decade, including the latest updates from ASH 2020 and discussed some of the challenges faced. Considering the current hits and misses of CAR T therapies, we provide a comprehensive analysis on the current manufacturing technologies, and deliberate on the future of CAR T-cell domain in MM.
Highlights
Multiple myeloma (MM), which accounts for 10% of blood cancers, is a malignancy of plasma cells originating in the bone marrow
A recent meta-analysis study on a total of 23 different B-cell maturation antigen (BCMA)-Chimeric antigen receptor (CAR) T-cell products that have been used in a total of 640 patients, reported an average overall response rate (ORR) of 80.5%, with 44.8% complete response (CR) and 12.2 months median PFS49
A novel anti-signaling lymphocytic activation molecule F7 (SLAMF7)/BCMA bispecific CAR T-cell product is under preclinical development with aim of increasing tumor coverage and overcoming antigen loss
Summary
Multiple myeloma (MM), which accounts for 10% of blood cancers, is a malignancy of plasma cells originating in the bone marrow. JNJ-4528, the bi-epitope CAR T-cell product containing two BCMA-targeting domains, aimed to enhance the antigen binding affinity, has shown an impressive 94.8% ORR in the CARTITUDE-1 trial[44,45]. A recent meta-analysis study on a total of 23 different BCMA-CAR T-cell products that have been used in a total of 640 patients, reported an average ORR of 80.5%, with 44.8% CR and 12.2 months median PFS49.
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