Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Axicabtagene Ciloleucel in Combination with Atezolizumab in Patients with Refractory Diffuse Large B-Cell Lymphoma: The Phase 1/2 ZUMA-6 Trial.
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Jacobson Caron A, Westin Jason R, Miklos David B, Herrera Alex F, Ritz Jerome, Rodig Scott, Arihara Yohei, Cao Subing, Sun Jennifer, Mao Daqin, Adhikary Sabina, Neumann Frank, Grechko Nikolay, Locke Frederick L
Аннотация
PURPOSE: Chimeric antigen receptor (CAR) T-cell therapies have improved outcomes in patients with relapsed/refractory large B-cell lymphoma (LBCL). However, up to two thirds of these patients do not maintain long-term responses. The phase 1/2 ZUMA-6 study investigated the feasibility of combining the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with the PD-L1 inhibitor atezolizumab as a potential approach to increase treatment efficacy while maintaining acceptable safety.
PATIENTS AND METHODS: Patients with refractory diffuse LBCL received a single axi-cel infusion (2 × 106 cells/kg), followed by atezolizumab 1,200 mg i.v. every 21 days for four cycles. Primary endpoints were dose-limiting toxicities (phase 1) and complete response rate (phase 2). Other efficacy and safety outcomes and pharmacokinetics/pharmacodynamics were assessed.
RESULTS: Overall, 34 patients received axi-cel plus atezolizumab in ZUMA-6. The median follow-up for the final analysis was 56.9 months. In phase 1, one patient experienced dose-limiting toxicities (grade 4 neutropenia and thrombocytopenia). Thirty patients (88%) experienced grade ≥3 treatment-emergent adverse events. Three (9%) and 11 (32%) patients experienced grade ≥3 cytokine release syndrome and neurologic events, respectively. In the final analysis, 15 patients (54%) had a complete response. The median progression-free survival and overall survival were 9 and 32.2 months, respectively. Peak CAR T-cell and cytokine profiles were comparable with those previously reported for axi-cel monotherapy (ZUMA-1).
CONCLUSIONS: Axi-cel plus atezolizumab had a manageable safety profile, with no new safety signals. Safety and efficacy of this combination were consistent with axi-cel monotherapy. Correlative analyses could inform with regard to which patients with LBCL may benefit from axi-cel and immune checkpoint inhibitor combinations.
PATIENTS AND METHODS: Patients with refractory diffuse LBCL received a single axi-cel infusion (2 × 106 cells/kg), followed by atezolizumab 1,200 mg i.v. every 21 days for four cycles. Primary endpoints were dose-limiting toxicities (phase 1) and complete response rate (phase 2). Other efficacy and safety outcomes and pharmacokinetics/pharmacodynamics were assessed.
RESULTS: Overall, 34 patients received axi-cel plus atezolizumab in ZUMA-6. The median follow-up for the final analysis was 56.9 months. In phase 1, one patient experienced dose-limiting toxicities (grade 4 neutropenia and thrombocytopenia). Thirty patients (88%) experienced grade ≥3 treatment-emergent adverse events. Three (9%) and 11 (32%) patients experienced grade ≥3 cytokine release syndrome and neurologic events, respectively. In the final analysis, 15 patients (54%) had a complete response. The median progression-free survival and overall survival were 9 and 32.2 months, respectively. Peak CAR T-cell and cytokine profiles were comparable with those previously reported for axi-cel monotherapy (ZUMA-1).
CONCLUSIONS: Axi-cel plus atezolizumab had a manageable safety profile, with no new safety signals. Safety and efficacy of this combination were consistent with axi-cel monotherapy. Correlative analyses could inform with regard to which patients with LBCL may benefit from axi-cel and immune checkpoint inhibitor combinations.