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） 后取得了惊人的结果，但大多数患者最终会复发。关于 BCMA 定向 CAR T 细胞治疗后复发后的挽救治疗的数据有限。在这里，我们分析了 CAR T 细胞治疗后复发的结果和不同挽救策略的影响，该队列由 139 名接受 talquetamab （n = 28）、teclistamab （n = 37）、免疫调节药物 （IMiD）、蛋白酶体抑制剂 （PI） 或 CD38 单克隆抗体 （n = 43） 和其他 （n = 43） 和其他 （n= 31）。CAR T 细胞治疗后中位复发时间为 5 个月，53% 的患者在复发时患有髓外疾病 （EMD），与复发后结局不佳相关 （P = 0.005）。talquetamab 挽救治疗后的总体缓解和完全缓解分别为 79% 和 39%，teclistamab 分别为 64% 和 32%，IMiDs/PIs/CD38 分别为 30% 和 0%，其他为 26% 和 3% （P < 0.001）。双特异性抗体显著改善了反应持续时间和中位生存期 （P < 0.001）。双特异性抗体似乎克服了与早期复发和 EMD 相关的不良预后，并且是多变量分析中提高生存率的独立预测因子。总之，这些结果表明双特异性抗体是 RRMM CAR T 细胞治疗后复发的护理标准。