Department of Hematology, Centre Hospitalo-Universitaire (CHU) Lille.
INSERM U1286, Infinite.
Blood Adv. 2021 Aug 10;5(15):3016-3020. doi: 10.1182/bloodadvances.2021004176.
The recent emergence of anti-B-cell maturation antigen (BCMA) therapies holds great promise in multiple myeloma (MM). These include chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates. Their development in clinical trials and further approval are changing the strategy for treating MM. Considering that a cure has not been reached, a central question in the coming years will be the possibility of using these therapies sequentially. Here, we report 2 cases of the serial use of anti-BCMA therapies with parallel monitoring of BCMA expression and anti-CAR antibodies. We further discuss recent data from clinical studies that have informed us about the different mechanisms of resistance to anti-BCMA therapies, including antigen escape, BCMA shedding, anti-drug antibodies, T-cell exhaustion, and the emergence of an immunosuppressive microenvironment. This knowledge will be essential to help guide the strategy of serial treatments with anti-BCMA therapies.
近期出现的抗 B 细胞成熟抗原（BCMA）疗法在多发性骨髓瘤（MM）中具有广阔的应用前景。这些疗法包括嵌合抗原受体（CAR）T 细胞、双特异性抗体和抗体药物偶联物。它们在临床试验中的发展和进一步的批准正在改变 MM 的治疗策略。考虑到尚未达到治愈效果，未来几年的一个核心问题将是是否有可能依次使用这些疗法。在此，我们报告了 2 例抗 BCMA 疗法的序贯使用案例，并平行监测了 BCMA 表达和抗 CAR 抗体。我们进一步讨论了来自临床研究的最新数据，这些数据为我们提供了有关抗 BCMA 疗法耐药的不同机制的信息，包括抗原逃逸、BCMA 脱落、抗药物抗体、T 细胞耗竭以及免疫抑制微环境的出现。这些知识对于指导抗 BCMA 疗法的序贯治疗策略至关重要。
