Data describing outcomes of teclistamab in multiple myeloma patients with prior exposure to BCMA-directed therapy (BCMA-DT) are limited. The goal of this multicenter retrospective analysis was to report the efficacy and safety of standard-of-care teclistamab in patients with prior BCMA-DT. A total of 385 patients were included, of whom 193 (50%) had received prior BCMA-DT, including 47 (24%) patients with prior antibody-drug conjugate (ADC)-only, 99 (51%) with chimeric antigen receptor T-cell therapy (CAR T)-only, 36 (19%) with both ADC and CAR T, 6 (3%) with bispecific antibody-only, and 5 (3%) with other combinations. Most safety parameters between cohorts were comparable. The prior BCMA-DT cohort had a lower overall response rate (ORR: 48.7% versus 61.5%; p = 0.012), and median progression-free survival (PFS: 4.6 versus 8.2 months; p = 0.017) compared to the cohort without prior BCMA-DT. However, in multivariable analysis, despite a clear trend, ultimately receipt of a prior BCMA-DT was not independently associated with ORR or PFS (p = 0.057 and p = 0.1, respectively). No significant differences in PFS were noted when stratifying patients by number of prior BCMA-DTs, types of all prior BCMA-DTs received, type of most recent prior BCMA-DT, or depth of response to most recent BCMA-DT. Using the maximally selected rank statistics method, the optimal cut-off for time from the last BCMA-DT exposure to teclistamab initiation was identified as 8.7 months. Patients with >8.7 months between their last exposure to prior BCMA-DT and teclistamab initiation had a significantly improved median PFS with teclistamab (8.1 months, 95% CI: 4.6–11.7) compared to patients with <8.7 months (2.5 months, 95% CI: 1.1–5.7), p = 0.001. Altogether, our findings support the use of teclistamab as a viable treatment option in patients previously exposed to BCMA-DT.
目前描述teclistamab在既往接受过BCMA靶向治疗的复发难治性多发性骨髓瘤患者中疗效的数据仍有限。这项多中心回顾性分析旨在报告标准治疗方案teclistamab在既往接受过BCMA靶向治疗的患者中的有效性和安全性。研究共纳入385例患者，其中193例（50%）曾接受过BCMA靶向治疗，包括47例（24%）仅接受过抗体药物偶联物治疗、99例（51%）仅接受过嵌合抗原受体T细胞疗法、36例（19%）同时接受过上述两种治疗、6例（3%）仅接受过双特异性抗体治疗以及5例（3%）接受过其他联合治疗方案。两组间大多数安全性参数具有可比性。与未接受过BCMA靶向治疗的患者相比，既往接受过BCMA靶向治疗的患者总缓解率较低（48.7%对比61.5%；p=0.012），中位无进展生存期较短（4.6个月对比8.2个月；p=0.017）。然而，在多变量分析中，尽管存在明显趋势，但既往是否接受过BCMA靶向治疗最终并未显示出与总缓解率或无进展生存期的独立相关性（p值分别为0.057和0.1）。当按既往BCMA靶向治疗次数、所有既往BCMA靶向治疗类型、最近一次BCMA靶向治疗类型或对最近一次BCMA靶向治疗的反应深度进行分层分析时，无进展生存期均未观察到显著差异。通过最大选择秩统计方法，确定从末次BCMA靶向治疗结束至开始teclistamab治疗的最佳时间截点为8.7个月。末次BCMA靶向治疗与teclistamab起始间隔超过8.7个月的患者，其中位无进展生存期显著优于间隔短于8.7个月的患者（8.1个月，95% CI：4.6–11.7对比2.5个月，95% CI：1.1–5.7），p=0.001。总之，我们的研究结果支持teclistamab可作为既往接受过BCMA靶向治疗患者的一种可行治疗选择。
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