The treatment of multiple myeloma (MM) is evolving rapidly. In the past few years, chimeric antigen receptor (CAR) modified T-cell and bispecific antibody (BsAb) are bringing new treatment options to relapsed/refractory (RR) MM patients. Currently, B-cell maturation antigen (BCMA) has emerged as the most commonly used target of T-cell based immunotherapies for RRMM. Clinical data have demonstrated promising efficacy and manageable safety profile of both CAR T-cell and BsAb therapies in heavily pretreated RRMM. However, most patients suffer from relapses at later time points, and the resistance mechanism remains largely unknown. Theoretically, loss of antigen is a potential tumor intrinsic resistance mechanism against BCMA-targeted immunotherapies. Therefore, strategies to overcome this kind of drug resistance are needed for these patients. In this review, we will discuss the loss of BCMA in the new epoch of immunotherapy for MM.
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