Chimeric antigen receptor T‐cell therapy in multiple myeloma: A comprehensive review of current data and implications for clinical practice

Abstract

AbstractMultiple myeloma (MM) is a hematologic malignancy defined by the clonal proliferation of transformed plasma cells. Despite tremendous advances in the treatment paradigm of MM, a cure remains elusive for most patients. Although long‐term disease control can be achieved in a very large number of patients, the acquisition of tumor resistance leads to disease relapse, especially in patients with triple‐class refractory MM (defined as resistance to immunomodulatory agents, proteosome inhibitors, and monoclonal antibodies). There is an unmet need for effective treatment options in these patients. Chimeric antigen receptor (CAR) T‐cell therapy is a novel approach that has demonstrated promising efficacy in the treatment of relapsed, refractory MM (RRMM). These genetically modified cellular therapies have demonstrated deep and durable remissions in other B‐cell malignancies, and current efforts aim to achieve similar results in patients with RRMM. Early studies have demonstrated remarkable response rates with CAR T‐cell therapy in RRMM; however, durable responses with CAR T‐cell therapies in myeloma have yet to be realized. In this comprehensive review, the authors describe the development of CAR T‐cell therapies in myeloma, the outcomes of notable clinical trials, the toxicities and limitations of CAR T‐cell therapies, and the strategies to overcome therapeutic challenges of CAR T cells in the hope of achieving a cure for multiple myeloma.