Richardson Tim, Holtick Udo, Frenking Jan Hendrik, Tharmaseelan Hishan, Balke-Want Hyatt, Flümann Ruth, Mai Elias K, Sauer Sandra, Teipel Raphael, von Bonin Malte, Hallek Michael, Scheid Christoph, Gödel Philipp
Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne, University of Cologne, Germany.
Heidelberg University Hospital, Heidelberg, Germany.
Blood Adv. 2025 Jul 11. doi: 10.1182/bloodadvances.2025016712.
Multiple myeloma (MM) relapsing after BCMA-directed chimeric antigen receptor T-cell (CAR-T) treatment remains a therapeutic challenge. Data on re-exposure to CAR-T targeting the same antigen are scarce. We analyzed 10 heavily pretreated MM patients at three medical centers treated with the commercially approved CAR-T product ide-cel in a real-world setting. Upon relapse, all patients received cilta-cel as a second CAR-T infusion, with bridging treatments permitted between both therapies. Sequential therapy with BCMA-directed CAR-T therapy was safe, with no higher-grade immune cell-associated side effects or new safety signals. We found robust CAR-T expansion and high response rates (100% ³ VGPR with 60% achieving MRD-negativity) with an estimated progression-free survival 64.8% (95% CI: 39-100%) at 6 months after the second CAR-T treatment. Duration of response to first CAR-T therapy was predictive for durable responses to the second CAR-T product. Loss of BCMA antigen occurred in only one of three patients relapsing after cilta-cel. Two of three relapsing patients died within a year and showed no further response to bispecific antibody treatment. This study provides the first real-world evidence that sequential treatment with two different commercially approved BCMA CAR-T products is both feasible and effective, particularly in patients with prolonged responses to initial BCMA CAR-T therapy.
在接受靶向B细胞成熟抗原（BCMA）的嵌合抗原受体T细胞（CAR-T）治疗后复发的多发性骨髓瘤（MM）仍然是一个治疗挑战。关于再次使用靶向相同抗原的CAR-T的数据很少。我们分析了在三个医疗中心接受过大量预处理的10例MM患者，这些患者在真实世界环境中接受了商业批准的CAR-T产品ide-cel治疗。复发后，所有患者均接受西达基奥仑赛作为第二次CAR-T输注，两种治疗之间允许进行桥接治疗。序贯使用靶向BCMA的CAR-T治疗是安全的，没有更高级别的免疫细胞相关副作用或新的安全信号。我们发现CAR-T有强劲的扩增且缓解率高（100%≥非常好的部分缓解[VGPR]，60%达到微小残留病阴性[MRD-]），在第二次CAR-T治疗后6个月时估计无进展生存率为64.8%（95%置信区间：39-100%）。对首次CAR-T治疗的缓解持续时间可预测对第二种CAR-T产品的持久缓解。在接受西达基奥仑赛治疗后复发的3例患者中，只有1例出现BCMA抗原丢失。3例复发患者中有2例在1年内死亡，对双特异性抗体治疗无进一步反应。本研究提供了首个真实世界证据，即序贯使用两种不同的商业批准的靶向BCMA的CAR-T产品是可行且有效的，特别是对于对初始靶向BCMA的CAR-T治疗有持久反应的患者。
