决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Outcomes of CAR T-cell Therapy and Bispecific Antibodies as Single-Modality and Sequential Strategies in Relapsed/Refractory Multiple Myeloma.
无标签:我们通过一项针对640例复发/难治性多发性骨髓瘤患者的回顾性多中心研究的互补偏倚校正分析,探讨了单次或连续嵌合抗原受体(CAR)T细胞和双特异性抗体(BsAb)治疗模式与临床结局的相关性。
本研究通过对一项纳入640例复发或难治性多发性骨髓瘤患者的回顾性多中心研究进行互补性偏倚校正分析,探讨了单独或先后接受嵌合抗原受体(CAR)T细胞和双特异性抗体(BsAb)治疗与临床结局的关系。先后接受这两种治疗似乎可获得最有利的生存轨迹。以CAR-T治疗作为初始治疗〔伊德卡布他基因·维克鲁塞(idecabtagene vicleucel,ide-cel)、西达基奥仑赛(ciltacabtagene autoleucel,cilta-cel)或cesnicabtagene autoleucel(cesni-cel)〕与更长的缓解期相关。然而,无论初始采用哪种治疗方式,因早期疾病进展导致的死亡率均相近,这提示耐药可能抵消初始疗效差异。按产品分析,CAR-T的获益似乎主要由cilta-cel和cesni-cel驱动;而BsAb的结局至少与ide-cel相当。这些探索性发现凸显了治疗顺序对于优化长期结局的重要性,并强调应在不同医疗体系中确保患者能够公平、及时地获得这两种治疗方式。 意义:在这一真实世界队列中,以CAR-T作为初始治疗与更长的缓解期相关;先后采用两种治疗方式的序贯免疫治疗取得了最有利的结局。然而,早期治疗失败会抵消两种治疗方式之间的初始疗效差异。这些发现为开展前瞻性治疗顺序试验、并确保患者公平获得两种治疗提供了依据。另见Banerjee的相关评论,第650页。
UNLABELLED: We explored single or consecutive chimeric antigen receptor (CAR) T and bispecific antibody (BsAb) treatment modalities as correlates of clinical outcomes, by complementary bias-correction analysis of a retrospective multicenter study of 640 patients with relapsed/refractory multiple myeloma. The sequential use of both modalities seemed to yield the most favorable survival trajectories. Initiating treatment with CAR T [idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel), cesnicabtagene autoleucel (cesni-cel)] was associated with longer remission. However, mortality from early progression was similar regardless of initial modality, suggesting that resistance may negate initial efficacy difference. On the product level, the benefit of CAR T seemed to be driven by cilta-cel and cesni-cel, whereas BsAbs showed at least comparable outcomes with ide-cel. These exploratory findings highlight the critical importance of treatment sequencing in optimizing long-term outcomes and underscore the need for equitable and timely access to both modalities across healthcare systems. SIGNIFICANCE: In this real-world cohort, initiating treatment with CAR T was associated with longer remission, and sequential immunotherapy incorporating both modalities yielded the most favorable outcomes. However, early treatment failure negated initial efficacy differences between modalities. These findings provide a rationale for prospective sequencing trials and equitable access to both treatments. See related commentary by Banerjee, p. 650.
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