ZUMA-14 phase II results: Axi-cel + rituximab for refractory LBCL

Results from the phase II, open-label, single-arm ZUMA-14  trial (NCT04002401), investigating axicabtagene ciloleucel (axi-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, + rituximab, a CD20-targeting monoclonal antibody, in adults with chemorefractory large B-cell lymphoma (LBCL), were published in Nature Cancer by Strati et al. (N = 26; modified intention-to-treat [mITT]). The primary endpoint was investigator-assessed complete response (CR) rate. 

Key data: The objective response rate (ORR) was 88%, with a CR reported in 73% of patients (95% confidence interval [CI], 52–88%). At data cutoff, 46% of participants had an ongoing response (all had a CR), and 42% relapsed. Median duration of response (DoR) was 26.0 months (95% CI, 2.6–not estimable [NE]) and median progression-free survival (PFS) was 23.6 months (95% CI, 3.4–NE); median overall survival (OS) was not reached (95% CI, 25.8–NE). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 92% of patients; cytokine release syndrome (CRS) occurred in 96% (all Grade 1–2) and neurologic events in 62% (Grade 3, 15%) of patients.

Key learning: Axi-cel + rituximab demonstrated durable efficacy with no new safety signals, supporting dual CD19/CD20 targeting as a feasible strategy to potentially limit antigen escape in refractory LBCL.