A better understanding of the roles of the adaptive and innate immune systems in the oncogenesis of cancers including multiple myeloma (MM) has led to the development of novel immune-based therapies. B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D) and Fc receptor-like protein 5 (FcRL5, also known as FcRH5) are cell-surface transmembrane proteins expressed by plasma cells, and have been identified as prominent immunotherapeutic targets in MM, with promising activity demonstrated in patients with heavily pretreated relapsed and/or refractory disease. Indeed, since 2020, antibody–drug conjugates, bispecific T cell engagers and autologous chimeric antigen receptor T cells targeting BCMA or GPRC5D have been approved for the treatment of relapsed and/or refractory MM. However, responses to these therapies are not universal, and acquired resistance invariably occurs. In this Review, we discuss the various immunotherapeutic approaches targeting BCMA, GPRC5D and FcRL5 that are currently either available or in clinical development for patients with MM. We also review the mechanisms underlying resistance to such therapies, and discuss potential strategies to overcome these mechanisms and improve patient outcomes.

更好地了解适应性和先天免疫系统在包括多发性骨髓瘤 （MM） 在内的癌症肿瘤发生中的作用，导致了基于免疫的新型疗法的开发。B 细胞成熟抗原 （BCMA）、G 蛋白偶联受体家族 C 组 5 成员 D （GPRC5D） 和 Fc 受体样蛋白 5 （FcRL5，也称为 FcRH5）是由浆细胞表达的细胞表面跨膜蛋白，已被确定为 MM 中的重要免疫治疗靶点，在既往接受过大量治疗的复发和/或难治性疾病患者中显示出有希望的活性。事实上，自 2020 年以来，靶向 BCMA 或 GPRC5D 的抗体-药物偶联物、双特异性 T 细胞接合剂和自体嵌合抗原受体 T 细胞已被批准用于治疗复发和/或难治性 MM。然而，对这些疗法的反应并不普遍，并且总是会出现获得性耐药。在本综述中，我们讨论了目前可用于 MM 患者或正在临床开发的针对 BCMA 、 GPRC5D 和 FcRL5 的各种免疫治疗方法。我们还回顾了对此类疗法耐药的潜在机制，并讨论了克服这些机制和改善患者预后的潜在策略。