Axicabtagene Ciloleucel Plus Atezolizumab Demonstrates Durable Clinical Activity in Relapsed or Refractory Large B-Cell Lymphoma
Clinical Summary:
-
Design/Population: The phase 1/2 ZUMA-6 trial evaluated axicabtagene ciloleucel in combination with atezolizumab in patients with relapsed or refractory large B-cell lymphoma, with primary end points of dose-limiting toxicities and complete response rate.
-
Key Outcomes: After nearly 5 years of follow-up, the combination demonstrated durable clinical activity, with a complete response rate of 54%, median progression-free survival of 9 months, and median overall survival of 32.2 months. Safety outcomes, including cytokine release syndrome and neurologic events, were consistent with the known safety profile of axicabtagene ciloleucel.
-
Clinical Relevance: These findings support the feasibility of combining PD-L1 blockade with CD19-directed CAR T-cell therapy and provide a rationale for continued investigation of checkpoint inhibitor combinations to improve long-term outcomes in large B-cell lymphoma.
Results from the phase 1/2 ZUMA-6 trial demonstrated that axicabtagene ciloleucel plus atezolizumab produced durable clinical activity with a manageable long-term safety profile in patients with relapsed or refractory large B-cell lymphoma.
“[CAR] T-cell therapies have improved outcomes in patients with relapsed/refractory large B-cell lymphoma... however, up to two thirds of these patients do not maintain long-term responses,” stated Caron Jacobson, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors. Here, researchers "investigated the feasibility of combining the CD19-directed CAR T-cell therapy axicabtagene ciloleucel with the PD-L1 inhibitor atezolizumab as a potential approach to increase treatment efficacy while maintaining acceptable safety.”
In this trial, 34 patients with relapsed or refractory large B-cell lymphoma received a single infusion of axicabtagene ciloleucel (2 × 10⁶ CAR T cells/kg) followed by 1200 mg of atezolizumab administered intravenously every 21 days for 4 cycles. The primary end points were dose-limiting toxicities and complete response rate. Key secondary end points included progression-free survival (PFS) and overall survival (OS).
After a median follow-up of 56.9 months, grade 4 dose-limiting neutropenia and thrombocytopenia were each reported in 1 patient. Grade ≥3 treatment-emergent adverse events occurred in 88% of patients. Grade ≥3 cytokine release syndrome occurred in 9% of patients, and grade ≥3 neurologic events occurred in 32% of patients.
A complete response was achieved in 54% of patients. Median PFS was 9 months, and median OS was 32.2 months. Peak CAR T-cell expansion and cytokine profiles were comparable to those previously reported with axicabtagene ciloleucel monotherapy.
“Safety and efficacy of this combination were consistent with [axicabtagene ciloleucel] monotherapy,” concluded Dr Jacobson et al. “Correlative analyses could inform with regard to which patients with [large B-cell lymphoma] may benefit from [axicabtagene ciloleucel] and immune checkpoint inhibitor combinations.”
Source:
Jacobson CA, Westin JR, Miklos DB, et al. Axicabtagene ciloleucel in combination with atezolizumab in patients with refractory diffuse large B-cell lymphoma: The phase 1/2 ZUMA-6 trial. Clin Cancer Res. Published online: January 23, 2026. doi: 10.1158/1078-0432.CCR-25-0602
