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INTRODUCTION: Relapsed or refractory acute lymphoblastic leukemia (R/R ALL) remains a major therapeutic challenge with poor long-term survival outcomes. Although checkpoint inhibitors targeting PD-1/PD-L1 have shown efficacy in other hematologic malignancies, their role in ALL has not been fully defined. Combination strategies integrating PD-1/PD-L1 blockade with chemotherapy or CAR-T cells may enhance anti-leukemic responses and overcome immune resistance. METHODS: 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. RESULTS: 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. CONCLUSION: Adding PD-1 or PD-L1 blockade to either chemotherapy or CAR-T therapy improved clinical outcomes without excess toxicity in R/R ALL.
Zou et al. (Fri,) studied this question.