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