嵌合抗原受体 T 细胞治疗复发/难治性 B 细胞非霍奇金淋巴瘤患者后维持程序性细胞死亡 1 抑制剂的疗效。

IF 4.9 2区医学 Q2 CELL BIOLOGY Cellular Oncology Pub Date : 2024-08-01 Epub Date: 2024-04-02 DOI:10.1007/s13402-024-00940-y

Xiangke Xin, Xiaojian Zhu, Yang Yang, Na Wang, Jue Wang, Jinhuan Xu, Jia Wei, Liang Huang, Miao Zheng, Yi Xiao, Chunrui Li, Yang Cao, Fankai Meng, Lijun Jiang, Yicheng Zhang

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引用次数: 0

摘要

导言：嵌合抗原受体（CAR）-T细胞在约30%至40%的复发/难治性（r/r）B细胞非霍奇金淋巴瘤（B-NHL）中获得了长期耐受性。CAR-T治疗后的维持治疗是必要的，而PD1抑制剂是重要的维持治疗选择之一：从2019年3月到2022年7月，共有173名r/r B-NHL患者在CD19/22 CAR-T疗法单独或与自体造血干细胞移植（ASCT）联合治疗后接受了PD1抑制剂维持治疗，他们接受了两项试验的资格评估。共有81名患者接受了PD1抑制剂维持治疗：在CD19/22 CAR-T疗法试验中，PD1抑制剂维持治疗组的客观反应率（ORR）（82.9% vs 60%；P = 0.04）和2年无进展生存期（PFS）（59.8% vs 21.3%；P = 0.001）均优于非维持治疗组。两组的估计两年总生存期（OS）相当（60.1% vs 45.1%；P = 0.112）。两组的CD19 CAR-T和CD22 CAR-T峰值扩增水平无差异。PD1抑制剂维持组CD19和CD22 CAR-T的持续时间长于非维持组。在CD19/22 CAR-T疗法联合ASCT试验中，非维持治疗组和PD1抑制剂维持治疗组的ORR（81.4% vs 84.8%；P = 0.67）、2年PFS（72.3% vs 74.9%；P = 0.73）和2年OS（84.1% vs 80.7%；P = 0.79）均无显著差异。CD19和CD22 CAR-T的峰值扩增水平和持续时间在两组之间没有统计学差异。在使用PD1抑制剂维持治疗期间，所有不良事件均可控。在多变量分析中，类型和R3m是影响CAR-T治疗后使用PD1抑制剂维持治疗的r/r B-NHL患者OS的独立预测因素：结论：CD19/22 CAR-T治疗后使用PD1抑制剂维持治疗可为r/r B-NHL患者带来更好的反应和生存率，但在CD19/22 CAR-T细胞治疗联合ASCT试验中则没有这种效果。

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Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.

Introduction: Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options.

Methods: A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy.

Results: In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy.

Conclusion: PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.

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来源期刊

Cellular Oncology ONCOLOGY-CELL BIOLOGY

CiteScore

10.30

自引率

1.50%

发文量

审稿时长

12 months

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.