Tan Chia Jie, Kacerek Dylan, Kampirapawong Nattawara, Godara Amandeep, Chaiyakunapruk Nathorn
Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.
University of Phayao, Phayao, Thailand.
Cancer Med. 2025 Mar;14(5):e70585. doi: 10.1002/cam4.70585.
There is a lack of clear guidance on the appropriate next choice of therapy for patients with relapsed/refractory multiple myeloma who become refractory to daratumumab, an anti-CD38 antibody. This review aims to identify and compare treatments with published clinical trial evidence among patients with daratumumab-refractory multiple myeloma.
MEDLINE, Cochrane CENTRAL, and EMBASE databases were searched for clinical trials that evaluated treatments for patients with multiple myeloma who were refractory to daratumumab from November 2015 to October 2023. Eligible studies may have enrolled only patients who were refractory to daratumumab or reported findings on patients with daratumumab-refractory disease in subgroup analyses. Treatment outcomes of interest included response rates and survival outcomes. Screening and data extraction were done independently by two reviewers using covidence, and any discrepancy was resolved by a third reviewer. Qualitative synthesis was performed to describe and compare patient outcomes associated with different treatments.
A total of 33 papers/published studies, representing 23 clinical trials, were eligible/included. Interventions from the eligible trials include chimeric antigen receptor (CAR)-T cell therapy, B-cell maturation antigen (BCMA)-directed antibodies, other monoclonal antibodies, cereblon E3 ligase modulators, a peptide-drug conjugate, and other targeted therapies. CAR T-cell therapy demonstrated the highest overall response rates, longer median overall, and progression-free survival in addition to significantly lower risk of death and higher odds of response compared to standard of care. Similarly, high response rates and/or long-term survival was also observed for other BCMA-directed treatments, such as elranatamab and teclistamab.
Based on the results of this systematic review, BCMA-directed therapies such as CAR-T cell therapy and bispecific antibodies demonstrate promising efficacy among patients with anti-CD38 refractory disease. However, additional evidence from randomized clinical trials is necessary to establish best practice guidelines.
对于复发/难治性多发性骨髓瘤患者，在对抗CD38抗体达雷妥尤单抗产生耐药后，缺乏关于合适的下一步治疗选择的明确指导。本综述旨在识别并比较已发表的临床试验证据中针对达雷妥尤单抗耐药的多发性骨髓瘤患者的治疗方法。
检索MEDLINE、Cochrane CENTRAL和EMBASE数据库，查找2015年11月至2023年10月期间评估针对对达雷妥尤单抗耐药的多发性骨髓瘤患者治疗方法的临床试验。符合条件的研究可能仅纳入了对达雷妥尤单抗耐药的患者，或在亚组分析中报告了对达雷妥尤单抗耐药疾病患者的研究结果。感兴趣的治疗结果包括缓解率和生存结果。两名审阅者使用covidence独立进行筛选和数据提取，任何差异由第三名审阅者解决。进行定性综合分析以描述和比较与不同治疗相关的患者结果。
共有33篇论文/已发表研究，代表23项临床试验，符合条件/被纳入。符合条件的试验中的干预措施包括嵌合抗原受体（CAR）-T细胞疗法、靶向B细胞成熟抗原（BCMA）的抗体、其他单克隆抗体、脑啡肽E3连接酶调节剂、一种肽-药物偶联物以及其他靶向疗法。与标准治疗相比，CAR T细胞疗法显示出最高的总体缓解率、更长的中位总生存期和无进展生存期，此外死亡风险显著降低，缓解几率更高。同样，对于其他靶向BCMA的治疗，如埃罗妥珠单抗和替西妥单抗，也观察到了高缓解率和/或长期生存。
基于本系统综述的结果，CAR-T细胞疗法和双特异性抗体等靶向BCMA的疗法在抗CD38耐药疾病患者中显示出有前景的疗效。然而，需要来自随机临床试验的更多证据来制定最佳实践指南。
