Three-Year Follow-Up Analysis of Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5).

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 CAR T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel in patients with R/R indolent non-Hodgkin lymphoma (iNHL; N=104), including FL and marginal zone lymphoma (MZL). In the primary analysis (17.5 months median follow-up), overall response rate (ORR) was 92% (74% complete response rate). Here we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2×106 CAR T cells/kg). The primary endpoint was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n=127) and 31.8 months in MZL (n=31), ORR was comparable to the primary analysis (94% in FL; 77% in MZL). Median progression-free survival was 40.2 months in FL and not yet reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest occurring since the prior analysis were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study is registered at ClinicalTrials.gov (NCT NCT03105336).