PD-1/PD-L1 抑制剂联合化疗或 CAR-T 细胞治疗复发/难治性急性淋巴细胞白血病的疗效与安全性：一项多中心 II 期试验

In this multicenter, open-label Phase II trial, 168 patients with R/R ALL were randomized to receive either FLAG chemotherapy plus nivolumab (Group A), CD19-directed CAR-T cells plus atezolizumab (Group B), or FLAG alone (Control). The primary endpoint was progression-free survival (PFS); secondary outcomes included overall survival (OS), MRD negativity, and safety. Immune profiling assessed biomarkers like PD-L1, TIM-3, CD25 + , and cytokines.

MRD negativity rates were significantly higher in experimental arms compared to control (Group A: 19.5 %; Group B: 27.8 %; Control: 3 %; p < 0.001). Median PFS was 7.7 months in Group A, 11.7 months in Group B, and 4.1 months in the control group (p < 0.001). Median OS was 10.75, 13.5, and 5.65 months, respectively (p < 0.001). Higher baseline PD-L1 expression was independently associated with improved survival (HR 0.90 per 10 % increase; p = 0.002). The addition of checkpoint inhibitors did not significantly increase severe toxicities, and infection rates were lower in experimental groups compared to control. The swimmer plot analysis demonstrated prolonged remission in MRD-negative patients.

Adding PD-1 or PD-L1 blockade to either chemotherapy or CAR-T therapy improved clinical outcomes without excess toxicity in R/R ALL.