Multiple myeloma (MM), despite therapeutic advances, remains an incurable disease. Therefore, the most patients eventually progress to relapsed/refractory multiple myeloma (RRMM). Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) has shown remarkable efficacy in RRMM. However, limitations such as antigen escape, tumor heterogeneity, and T-cell exhaustion led to relapse. This review provides a comprehensive perspective on the transformative potential of bispecific CAR-T cell therapy as a promising strategy to overcome resistance and improve outcomes for patients with RRMM. The mechanisms of resistance to BCMA-targeted CAR-T therapy are comprehensively analyzed and categorized into BCMA-positive and BCMA-negative relapse/refractory mechanisms. The MIF/CD74 pathway as a potential contributor to BCMA CAR-T resistance was supported by single-cell RNA sequencing data and previous studies. The mechanistic advantages of dual-target are explored dual target CAR-T can prevent antigen escape and enhance T-cell activation. Clinical review of clinical trial data demonstrates the superior efficacy of bispecific CAR-T compared to BCMA CAR-T, including higher drug effect and more manageable side effects.
Nasrudin Abd Rahim (Fri,) studied this question.