Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, The Netherlands.
Expert Opin Biol Ther. 2024 Sep;24(9):889-901. doi: 10.1080/14712598.2024.2397436. Epub 2024 Sep 1.
T-cell redirecting bispecific antibodies (BsAbs), targeting B-cell maturation antigen (BCMA) or G-protein - coupled receptor class C group 5 member D (GPRC5D), are efficacious new agents for the treatment of patients with relapsed or refractory MM.
This review discusses the pharmacokinetic properties, efficacy, and safety profile of T-cell redirecting BsAbs in MM, with a special focus on their optimal dosing schedule, resistance mechanisms and future strategies to enhance efficacy, reduce toxicity, and maximize duration of response.
To further improve the efficacy of BsAbs, ongoing studies are investigating whether combination therapy can enhance depth and duration of response. An important open question is also to what extent response to BsAbs can be improved when these agents are used in earlier lines of therapy. In addition, more evidence is needed on rational de-intensification strategies of BsAb dosing upon achieving a sufficient response, and if (temporary) treatment cessation is possible in patients who have achieved a deep remission (e.g. complete response or minimal residual disease-negative status).
靶向 B 细胞成熟抗原(BCMA)或 G 蛋白偶联受体 C 族 5 成员 D(GPRC5D)的 T 细胞重定向双特异性抗体(BsAbs)是治疗复发性或难治性多发性骨髓瘤患者的有效新型药物。
本文讨论了 T 细胞重定向 BsAbs 在多发性骨髓瘤中的药代动力学特性、疗效和安全性概况,特别关注其最佳剂量方案、耐药机制以及提高疗效、降低毒性和最大限度延长缓解期的未来策略。
为了进一步提高 BsAbs 的疗效,正在进行的研究探讨联合治疗是否可以增强反应的深度和持久性。一个重要的悬而未决的问题是,在早期治疗线中使用这些药物时,BsAbs 治疗的反应能在多大程度上得到改善。此外,在获得足够的反应后,关于 BsAb 剂量的合理减量化策略的更多证据,以及在达到深度缓解(例如完全缓解或微小残留病阴性状态)的患者中是否可以(暂时)停止治疗,也是有必要的。