Abstract
Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target. Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BITEs) and chimeric antigen receptor (CAR) T cell therapy. Current results of representative BCMA trials may close the gap of the unmet clinical need to further improve the outcome of heavily pretreated MM patients with the potency to change the paradigm in newly diagnosed and refractory MM. This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials.
Highlights
Multiple myeloma (MM) is the second most common hematological malignancy with substantial improvements in outcome due to introduction of novel therapeutic agents such as proteasome inhibitors (PIs; bortezomib, carfilzomib, ixazomib) and immunomodulatory agents (IMiDs; thalidomide, lenalidomide, pomalidomide) [1]
The ORR all over the dose escalation was 31%, but in patients (10/42) with the maximum tolerable dose (MTD) dose of 400 μg/day, the ORR was pronounced increased with 70%
The discovery of B-cell maturation antigen (BCMA) offers a new era in the field of immunotherapy in anti-myeloma therapy, including antibody-drug conjugates (ADCs), anti-BCMA/CD3 bispecific antibodies or anti-BCMA chimeric antigen receptor (CAR)-T cell therapy
Summary
Multiple myeloma (MM) is the second most common hematological malignancy with substantial improvements in outcome due to introduction of novel therapeutic agents such as proteasome inhibitors (PIs; bortezomib, carfilzomib, ixazomib) and immunomodulatory agents (IMiDs; thalidomide, lenalidomide, pomalidomide) [1]. The increased understanding of the pathophysiology of MM revealed in 2015 the first two immunotherapeutic agents—the monoclonal antibodies (mAbs) targeting CD38 antigen and signaling lymphocytic activation molecule family member 7 (SLAMF7) on the surface of MM cells—and enlarged standard therapeutic regimens in relapsed or refractory MM (RRMM) [2,3,4]. New generations of IMIDs and PIs have become available, the management of these MM patients remains challenging for the clinicians [10]; novel treatment modalities for RRMM disease to target current available MM therapies are indispensable. In the therapeutic landscape of MM therapy, B-cell maturation antigen (BCMA)—one of the most specific and highly expressed antigen on myeloma cells—offers a promising target in RRMM. The following review will highlight current insights of BCMA-targeted therapy options, updated efficacy and safety from current clinical trials, and their future clinical implication in the treatment of MM patients
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