Despite the astonishing outcomes after chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory multiple myeloma (RRMM), most patients eventually relapse. There are only limited data available on salvage therapies following relapse after BCMA-directed CAR T-cell therapy. Here, we analyzed outcomes of post-CAR T-cell therapy relapse and impact of different salvage strategies in an international cohort of 139 patients (n = 130 ide-cel, n = 9 cilta-cel), receiving talquetamab (n = 28), teclistamab (n = 37), combinations of immunomodulating drugs (IMiDs), proteasome inhibitors (PIs) or CD38 monoclonal antibodies (n = 43), and others (n = 31). The median time to relapse after CAR T-cell therapy was 5 months, 53% had the extramedullary disease (EMD) at relapse, associated with dismal post-relapse outcome (P = 0.005). Overall response and complete response upon salvage therapies were 79% and 39% for talquetamab, 64% and 32% for teclistamab, 30% and 0% for IMiDs/PIs/CD38, and 26% and 3% for others (P < 0.001). Duration of response, as well as median survival, was significantly improved with bispecific antibodies (P < 0.001, respectively). Bispecific antibodies seemed to overcome the poor prognosis associated with early relapse and EMD, and were independent predictors for improved survival in multivariable analysis. In summary, these results suggest bispecific antibodies as the standard of care for relapse after CAR T-cell therapy for RRMM.
尽管嵌合抗原受体（CAR）T细胞疗法治疗复发难治性多发性骨髓瘤（RRMM）取得了惊人成效，但多数患者最终仍会复发。目前关于BCMA靶向CAR-T细胞疗法后复发挽救治疗的数据十分有限。本研究分析了139例国际患者队列（其中130例接受ide-cel治疗，9例接受cilta-cel治疗）在CAR-T治疗后复发的结局及不同挽救策略的影响，治疗方案包括：talquetamab（28例）、teclistamab（37例）、免疫调节药物（IMiDs）/蛋白酶体抑制剂（PIs）/CD38单抗联合疗法（43例）及其他方案（31例）。CAR-T治疗后中位复发时间为5个月，53%患者在复发时伴有髓外病变（EMD），这与不良的复发后结局相关（P=0.005）。挽救治疗的总缓解率及完全缓解率分别为：talquetamab组79%和39%，teclistamab组64%和32%，IMiDs/PIs/CD38联合组30%和0%，其他方案组26%和3%（P<0.001）。双特异性抗体治疗显著改善了缓解持续时间及中位生存期（均P<0.001）。双特异性抗体似乎能克服早期复发和EMD相关的不良预后，在多变量分析中成为改善生存的独立预测因子。总之，这些结果表明双特异性抗体可作为RRMM患者CAR-T治疗后复发的标准治疗选择。
肿瘤(癌症)患者之家