Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P. R. China.
Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, 430030, P. R. China.
Cell Oncol (Dordr). 2024 Aug;47(4):1425-1440. doi: 10.1007/s13402-024-00940-y. Epub 2024 Apr 2.
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.
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.
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.
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.
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）患者中获得了长期持久性。CAR-T 后维持治疗是必要的，PD1 抑制剂是重要的维持治疗选择之一。
2019 年 3 月至 2022 年 7 月，共有 173 例接受 PD1 抑制剂维持治疗的 r/r B-NHL 患者，这些患者单独接受 CD19/22 CAR-T 治疗或与自体造血干细胞移植（ASCT）联合接受 CD19/22 CAR-T 治疗，符合两项试验的入组标准。有 81 例患者接受 PD1 抑制剂维持治疗。
在 CD19/22 CAR-T 治疗试验中，PD1 抑制剂维持组的客观缓解率（ORR）（82.9% vs 60%；P=0.04）和 2 年无进展生存率（PFS）（59.8% vs 21.3%；P=0.001）显著优于非维持组。两组的 2 年总生存率（OS）相当（60.1% vs 45.1%；P=0.112）。两组间 CD19 CAR-T 和 CD22 CAR-T 的峰值扩增水平无差异。PD1 抑制剂维持组中 CD19 和 CD22 CAR-T 的持续时间长于非维持组。在 CD19/22 CAR-T 治疗联合 ASCT 试验中，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。两组间 CD19 和 CD22 CAR-T 的峰值扩增水平和持续时间无统计学差异。在 PD1 抑制剂维持治疗期间，所有不良反应均可控。多变量分析显示，类型和 R3m 是影响 CAR-T 治疗后 r/r B-NHL 患者 PD1 抑制剂维持治疗的 OS 的独立预测因素。
PD1 抑制剂维持治疗可提高 r/r B-NHL 患者接受 CD19/22 CAR-T 治疗后的反应和生存，但在 CD19/22 CAR-T 细胞治疗联合 ASCT 的试验中并非如此。
