CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.
Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.
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CD19/22 CAR-T 治疗后采用 PD1 抑制剂维持治疗在复发/难治性 B-NHL 中获得更优的缓解和生存,但在 CD19/22 CAR-T 细胞治疗联合 ASCT 的试验中并非如此。
研究评估了173例r/r B-NHL患者参加两项试验的资格;这些患者于2019年3月至2022年7月接受CD19/22 CAR-T 治疗后给予PD-1抑制剂维持治疗,CAR-T 可单独使用或联合自体造血干细胞移植(ASCT)。其中81例接受PD-1抑制剂维持治疗。
在CD19/22 CAR-T 单独治疗试验中,与未接受维持治疗组相比,PD-1抑制剂维持组客观缓解率(ORR)更高(82.9% vs 60%;P=0.04),2年无进展生存率(PFS)也更高(59.8% vs 21.3%;P=0.001)。两组估计2年总生存率(OS)相近(60.1% vs 45.1%;P=0.112)。两组CD19 CAR-T 和CD22 CAR-T 的峰值扩增水平无差异;PD-1抑制剂维持组CD19和CD22 CAR-T 的持续时间更长。在CD19/22 CAR-T 联合ASCT试验中,未维持治疗组与PD-1抑制剂维持组的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。两组CD19和CD22 CAR-T 峰值扩增水平及持续时间无统计学差异。PD-1抑制剂维持治疗期间所有不良事件均可控制。多变量分析中,治疗类型和R3m是影响CAR-T 后接受PD-1抑制剂维持的r/r B-NHL患者OS的独立预测因素。
CD19/22 CAR-T 后使用PD-1抑制剂维持治疗可改善r/r B-NHL患者的应答和生存;但在CD19/22 CAR-T 联合ASCT试验中未观察到这一获益。
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.
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