Min Chao, Zhong Xiong, Cui Yue, Zhang Hanfu, Wang Qingming
Department of Hematology, 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxin, China.
Hrain Biotechnology Co. Ltd., Shanghai, China.
Front Pharmacol. 2025 Mar 17;16:1515555. doi: 10.3389/fphar.2025.1515555. eCollection 2025.
Over the past few decades, the landscape for multiple myeloma (MM) therapy has significantly advanced, largely due to the approval and introduction of new-generation proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). Despite these advancements, MM remains incurable. In March 2021, the U.S. FDA approved the chimeric antigen receptor T-cell (CAR-T) therapy idecabtagene vicleucel (ide-cel) for relapsed/refractory multiple myeloma (R/R MM), heralding the advent of cellular therapies for R/R MM. However, due to factors such as the downregulation or loss of tumor antigen expression, T-cell exhaustion, and the influence of the tumor immune microenvironment, most R/R MM patients inevitably experience relapse following CAR-T cell therapy. Consequently, salvage therapy in the post-CAR-T setting has emerged as a critical area of research. This review discusses the potential factors leading to CAR-T therapy failure in R/R MM patients and discusses subsequent salvage therapeutic strategies, offering recommendations for addressing treatment failure in this context.
在过去几十年里，多发性骨髓瘤（MM）的治疗格局有了显著进展，这在很大程度上得益于新一代蛋白酶体抑制剂（PIs）和免疫调节药物（IMiDs）的获批和应用。尽管有这些进展，MM仍然无法治愈。2021年3月，美国食品药品监督管理局（FDA）批准嵌合抗原受体T细胞（CAR-T）疗法idecabtagene vicleucel（ide-cel）用于复发/难治性多发性骨髓瘤（R/R MM），这标志着R/R MM细胞疗法的到来。然而，由于肿瘤抗原表达下调或缺失、T细胞耗竭以及肿瘤免疫微环境的影响等因素，大多数R/R MM患者在接受CAR-T细胞治疗后不可避免地会复发。因此，CAR-T治疗后的挽救治疗已成为一个关键的研究领域。本综述讨论了导致R/R MM患者CAR-T治疗失败的潜在因素，并探讨了后续的挽救治疗策略，为解决这一背景下的治疗失败问题提供建议。
