CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Evaluation of Real-World Studies on Management of Relapsed Multiple Myeloma After BCMA-Directed Therapy Failure from U.S. Academic Centers and USMIRC.
Evaluation of Real-World Studies on Management of Relapsed Multiple Myeloma After BCMA-Directed Therapy Failure from U.S. Academic Centers and USMIRC.
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靶向B细胞成熟抗原（BCMA）的疗法（BDT）已改变复发/难治性多发性骨髓瘤治疗，但治疗失败后的最佳排序仍未明确。我们评估了三项回顾性多中心分析的真实世界结局。研究1比较既往接受过BDT患者接受BCMA CAR-T 与BCMA T细胞衔接器（TCE）的疗效（n=95）；研究2比较既往接受和未接受BDT患者使用teclistamab的结局（n=164）；研究3考察talquetamab（一种靶向GPRC5D的TCE）在经多线治疗患者中的疗效（n=68）。CAR-T 疗效优于TCE（总缓解率[ORR] 79%比51%，p<0.001；中位总生存期[OS] 30比12个月，p=0.008）。
既往接受BDT的teclistamab患者ORR较低（53%比68%，p=0.02），中位无进展生存期（PFS）也较短（2.5比9.7个月，p=0.01）。在BDT后不足6个月给药，结局较差（PFS HR 2.5；OS HR 2.9）。既往接受BDT患者使用talquetamab的ORR为68.3%；若BDT后不足6个月给药，或BDT是紧邻的既往治疗，缓解率显著较低（分别为56.8%比84.6%及48%比80.6%）。T细胞重定向疗法之间间隔6个月可改善疗效和生存。BDT治疗后应尽可能优先采用CAR-T；再次挑战BDT前应间隔超过6个月；早期复发或BDT难治时可考虑非BCMA靶点。
B-cell maturation antigen (BCMA)-directed therapies (BDTs) have transformed relapsed/refractory multiple myeloma treatment, but optimal post-failure sequencing remains undefined.
We evaluated real-world outcomes from three retrospective, multicenter analyses. Study 1 compared BCMA CAR-T and BCMA T-cell engagers (TCEs) in BDT-exposed patients ( n = 95). Study 2 evaluated teclistamab in BDT-exposed versus BDT-na ve patients ( n = 164). Study 3 examined talquetamab (GPRC5D-targeting TCE) in heavily pretreated patients ( n = 68). CAR-T therapy achieved superior outcomes versus TCE (overall response rate [ORR] 79% vs. 51%, p < 0. 001; median overall survival [OS] 30 vs. 12 months, p = 0. 008). Teclistamab-treated BDT-exposed patients had lower ORR (53% vs. 68%, p = 0. 02) and shorter median progression-free survival (PFS; 2. 5 vs. 9. 7 months, p = 0.
01) compared with BDT-na ve patients. Administration < 6 months post-BDT showed inferior outcomes (hazard ratio [HR] 2. 5 for PFS; HR 2. 9 for OS). Talquetamab achieved an ORR of 68. 3% among BDT-exposed patients, with significantly lower response rates when administered < 6 months post-BDT or when BDT was the immediate preceding treatment (56.
8% vs. 84. 6% and 48% vs. 80. 6%, respectively). Treatment-free intervals of 6 months between T-cell-redirecting therapies improved efficacy and survival. Post-BDT sequencing should prioritize CAR-T therapy when feasible, allow >6-month intervals before BDT re-challenge, and utilize non-BCMA targets for early relapse or BDT-refractory disease.
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