Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma.

Abstract

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 with marginal zone lymphoma) after a median follow-up of 64.6 months. Patients underwent leukapheresis and received lymphodepleting chemotherapy and axi-cel (2 × 10⁶ CAR T cells/kg). The overall response rate was 90% (75% complete response rate). The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment and overall survival were not reached (NR). At data cutoff, 55% of patients were alive without requiring subsequent anticancer therapy. Median lymphoma-specific PFS in patients with FL was NR; 34% had progression or death due to lymphoma or study treatment. Notably, after 30 months postinfusion, progression or lymphoma-related deaths were rare. Late-onset toxicities were infrequent and largely unrelated to axi-cel. Durable response and prolonged survival in FL were associated with robust early CAR T-cell expansion and naïve product phenotype. These findings confirm sustained responses and manageable safety with axi-cel in the long term among patients with R/R iNHL and its potential as a curative therapy in FL.