Myeloma Division, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
Leuk Lymphoma. 2022 Dec;63(13):3032-3043. doi: 10.1080/10428194.2022.2113532. Epub 2022 Sep 5.
In recent years, the treatment landscape of multiple myeloma has continued to evolve with the introduction of novel immunotherapies. This progress has translated to improved overall survival for patients, but an unmet need remains in the heavily pretreated and high-risk subsets of patients. Emerging immunotherapies in the form of CAR-T cell therapies have been approved for multiple myeloma. However, CAR-T cell therapy has logistical limitations and there is a need for immunotherapies that are readily available, safe, and effective in RRMM. Currently, pending approval, there are many "off the shelf" bispecific antibodies being developed that target BCMA, GPRC5D, FcRH5 and other cell surface proteins. Preliminary efficacy data has suggested that these bispecific antibody therapies have similar response rates (∼50-80%) in heavily pretreated patients. Similarly, to CAR-T cell therapy, cytokine release syndrome and immune effector cell associated neurotoxicity syndrome are adverse events of key interest and incidence range from ∼40 to 90% and 3 to 20%, respectively. In this review, we highlight the various bispecific immunotherapies under development in the treatment of multiple myeloma with a focus on the data from clinical phase I and II studies.
近年来,随着新型免疫疗法的引入,多发性骨髓瘤的治疗格局不断发展。这一进展为患者带来了总体生存的改善,但在预处理量大和高危患者亚组中仍存在未满足的需求。以嵌合抗原受体 T 细胞疗法(CAR-T 细胞疗法)形式出现的新型免疫疗法已获批用于多发性骨髓瘤。然而,CAR-T 细胞疗法存在后勤限制,需要易于获得、安全且对 RRMM 有效的免疫疗法。目前,有许多“现成的”双特异性抗体正在开发中,这些抗体针对 BCMA、GPRC5D、FcRH5 和其他细胞表面蛋白。初步疗效数据表明,这些双特异性抗体疗法在预处理量大的患者中的反应率相似(约 50-80%)。与 CAR-T 细胞疗法类似,细胞因子释放综合征和免疫效应细胞相关神经毒性综合征是关键关注的不良事件,其发生率分别为约 40%至 90%和 3%至 20%。在这篇综述中,我们重点介绍了在多发性骨髓瘤治疗中正在开发的各种双特异性免疫疗法,并强调了来自 I 期和 II 期临床研究的数据。