Axicabtagene Ciloleucel Plus Atezolizumab Demonstrates Promise in Relapsed/Refractory Large B-Cell Lymphoma

Key Clinical Takeaways:

• Design/Population: ZUMA-6 is a phase 1/2 study evaluating axicabtagene ciloleucel combined with atezolizumab in patients with refractory diffuse large B-cell lymphoma, with primary end points of dose-limiting toxicities and complete response rate.
• Key Outcomes: With a median follow-up of nearly 5 years, the combination achieved a complete response rate of 54%, with median progression-free survival of 9 months and median overall survival of 32.2 months. Safety outcomes, including rates of cytokine release syndrome and neurologic events, were consistent with prior reports of axicabtagene ciloleucel alone.
• Clinical Relevance: These findings suggest that adding PD-L1 inhibition to CD19-directed CAR T-cell therapy is feasible and does not appear to introduce new safety concerns, supporting further investigation of combination strategies to improve durability of response in large B-cell lymphoma.

Results from the phase 1/2 ZUMA-6 trial demonstrated that the addition of atezolizumab to axicabtagene ciloleucel showed promising clinical activity among patients with relapsed or refractory large B-cell lymphoma (LBCL).

“Chimeric antigen receptor (CAR) T-cell therapies have improved outcomes in patients with relapsed/refractory [LBCL]... 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. “The phase 1/2 ZUMA-6 study 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 study, 34 patients were enrolled to receive a single infusion of axicabtagene ciloleucel (2 × 10⁶ CAR T cells/kg) followed by intravenous atezolizumab (1200 mg) administered every 21 days for 4 cycles. Primary end points included dose-limiting toxicities and complete response rate. Key secondary end points included progression-free survival (PFS) and overall survival (OS).

At a median follow-up of 56.9 months, grade 4 dose-limiting neutropenia and thrombocytopenia were reported in 1 patient. Grade ≥3 treatment-emergent adverse events occurred in 88% of patients. Grade ≥3 cytokine release syndrome was reported in 9% of patients, and grade ≥3 neurologic events were reported 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 with those previously reported for 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 LBCL 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