Abstract
Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the unmet clinical need. However, there are still several major hurdles to overcome. Here we discuss the recent advances of CAR T-cell therapy for MM with an emphasis on future directions and possible risks. Currently, CAR T-cell therapy for MM is at the first stage of clinical studies, and most studies have focused on CAR T cells targeting B cell maturation antigen (BCMA), but other antigens such as cluster of differentiation 138 (CD138, syndecan-1) are also being evaluated. Although this therapy is associated with side effects, such as cytokine release syndrome and neurotoxicity, and relapses have been observed, the benefit–risk balance and huge potential drive the ongoing clinical progress. To fulfill the promise of recent clinical trial success and maximize the potential of CAR T, future efforts should focus on the reduction of side effects, novel targeted antigens, combinatorial uses of different types of CAR T, and development of CAR T cells targeting more than one antigen.
Highlights
Multiple myeloma (MM) is a cancer of plasma cells that build up in the bone marrow
P-B-cell maturation antigen (BCMA)-101 is a chimeric antigen receptor (CAR) T-cell construct created by fusing an anti-BCMA CentyrinTM with a CD3ζ/4-1BB domain, which results in CARTyrin
Showed that A proliferation-inducing ligand (APRIL)-based CAR T cells can destroy MM cells expressing BCMA and TACI as well as only TACI. These results suggest that APRIL-based CAR T-cell therapy can be especially valuable in the case of BCMA downregulation
Summary
Multiple myeloma (MM) is a cancer of plasma cells that build up in the bone marrow. MM results in hypercalcemia, anemia, renal dysfunction, bone destruction, and bone marrow failure. One novel strategy to eliminate cancer is chimeric antigen receptor (CAR) T-cell therapy. Two CAR T-cell therapies have been approved by the US Food and Drug Administration (FDA) for the treatment of cancer patients: Axicabtagene ciloleucel (Yescarta® ) and tisagenlecleucel (Kymriah® ). Both of them target the cluster of differentiation 19 (CD19) antigen, and both treatments are approved for subsets of patients with relapsed or refractory large B-cell lymphoma. We discuss the recent advances of CAR T-cell therapy for MM with a focus on currently evaluated targeted antigens, future development directions, and possible adverse effects
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