Multicenter phase 1-2 trial of axicabtagene ciloleucel plus azetolizumab for refractory diffuse large B-cell lymphoma

CAR T-cell therapies have improved outcomes in patients with refractory large B-cell lymphoma; however, up to two-thirds of these patients do not maintain long-term responses. The multicenter phase 1-2 ZUMA-6 trial evaluated the combination of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) with the PD-L1 inhibitor atezolizumab for refractory DLBCL. Overal, 34 patients received the combination, with median duration of follow-up 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. Fifteen patients (54%) had a complete response. Median progression-free survival and overall survival were 9.0 months and 32.2 months, respectively. The authors conclude that axi-cel plus atezolizumab had a manageable safety profile, with no new safety signals. Correlative analyses could inform as to which LBCL patients may benefit from axi-cel and immune checkpoint inhibitor combinations.