Wang Zhen, Song Yanqi, Guo Honglei, Yan Yuting, Ma Lin, Liu Baoshan
Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin, 300052, Heping District, China.
Curr Treat Options Oncol. 2025 Feb;26(2):128-141. doi: 10.1007/s11864-025-01290-z. Epub 2025 Jan 31.
According to the guidelines, the primary treatment for multiple myeloma is still based on drugs such as carfilzomib, lenalidomide, or daratumumab. However, patients with relapsed/refractory multiple myeloma (RRMM) may be insensitive or develop resistance to the above therapeutic medications. Thus, formulating standardized and rational treatment regimens for such patients remains an area for consideration. Multidrug combinations are available for the therapy of patients with relapsed/refractory multiple myeloma to improve their clinical outcome and prevent the occurrence of multidrug resistance. For instance, combination therapy with immunomodulators, proteasome inhibitors, and CD38 monoclonal antibodies. With the development of genomics and molecular diagnostic technologies, RRMM has entered the era of precision therapy. Targeted immunotherapeutic drugs such as monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor-T (CAR-T) cells have shown promising clinical response rates and favorable safety profiles in several clinical and experimental studies. These cutting-edge medicinal treatments may provide new hope for a cure for RRMM. However, the choice of treatment regimen still needs to adhere to the principle of individualization. Generally, we recommend treatment with drugs of a new generation or novel mechanism of action for patients with RRMM who are first relapsed, such as next-generation proteasome inhibitors, next-generation immunomodulators, and CD38-based monoclonal antibody regimens. For multiple relapsed RRMM, we recommend choosing a combination regimen or participating in relevant clinical trials. Additionally, monoclonal antibodies have become the standard of care for patients with RRMM. With the introduction of CAR-T therapy, ADCs, and bispecific antibodies, RRMM patients are expected to achieve deep remissions and long-term survival again.
根据指南，多发性骨髓瘤的主要治疗方法仍然基于卡非佐米、来那度胺或达雷妥尤单抗等药物。然而，复发/难治性多发性骨髓瘤（RRMM）患者可能对上述治疗药物不敏感或产生耐药性。因此，为这类患者制定标准化、合理的治疗方案仍是一个需要考虑的领域。对于复发/难治性多发性骨髓瘤患者的治疗，可采用多药联合方案以改善其临床结局并预防多药耐药的发生。例如，免疫调节剂、蛋白酶体抑制剂和CD38单克隆抗体的联合治疗。随着基因组学和分子诊断技术的发展，RRMM已进入精准治疗时代。靶向免疫治疗药物，如单克隆抗体、双特异性抗体、抗体药物偶联物（ADC）和嵌合抗原受体T细胞（CAR-T），在多项临床和实验研究中显示出有前景的临床缓解率和良好的安全性。这些前沿药物治疗可能为RRMM的治愈带来新希望。然而，治疗方案的选择仍需坚持个体化原则。一般来说，对于首次复发的RRMM患者，我们建议使用新一代或具有新作用机制的药物进行治疗，如下一代蛋白酶体抑制剂、下一代免疫调节剂和基于CD38的单克隆抗体方案。对于多次复发的RRMM患者，我们建议选择联合方案或参与相关临床试验。此外，单克隆抗体已成为RRMM患者的标准治疗方法。随着CAR-T疗法、ADC和双特异性抗体的引入，RRMM患者有望再次实现深度缓解和长期生存。
