The autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel) yielded considerable and durable clinical benefits. It also demonstrated a manageable safety profile in patients with indolent non-Hodgkin lymphoma (iNHL), according to results from the primary analysis of ZUMA-5 presented at the 2021 Transplantation & Cellular Therapy (TCT) Meetings of the American Society of Blood and Marrow Transplantation (ASBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR).
ZUMA-5 (ClinicalTrials.gov Identifier: NCT03105336) is an ongoing phase 2, multicenter, single-arm study of axi-cel in adult patients with relapsed or refractory iNHL. Following leukapheresis and conditioning therapy, participants received a single infusion of axi-cel (2 × 106 CAR-T cells/kg).
The primary endpoint was ORR by central review (Lugano staging; when ≥80 patients with FL had ≥12 months follow-up), and secondary endpoints included rates of CR, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) as well as safety and CAR T cell levels.
As of March 12, 2020, 146 patients of an estimated 160 participants targeted for enrollment had received axi-cel. Of those, 124 (84.9%) had follicular lymphoma (FL) (grades 1-3a), while 22 (15.1%) had marginal zone lymphoma (MZL; nodal or extranodal). Patients had a median age of 61 years. Most (86%) had stage III/IV disease.
Additionally, 47% of patients had a high/poor risk prognostic index (≥3 FLIPI), and 49% had high tumor bulk (GELF). The median number of prior lines of therapy was 3, and 68% of patients were refractory to last prior treatment. Within the past 2 years, 55% had disease progression.
The drug product was successfully produced for all patients. Among evaluable patients (n = 104), the ORR was 92%, with a 76% CR rate after a median follow-up of 17.5 months (range, 1.4-31.6). The ORR was slightly higher in patients with FL (n = 84) at 94%, with an 80% CR rate, and lower in those with MZL (n = 20) at 85%, with a 60% CR rate. At the time of data cutoff, 62% of treated patients maintained ongoing responses. Patients had 12-month estimated rates of 72% for DOR, 74% for PFS, and 93% for OS.
The investigators reported grade ≥3 adverse events (AEs), which occurred in 85% of the FL group and in 95% of the MZL group (86% overall). Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs), most of which resolved by the time of data cutoff, occurred in 6% and 15% of the FL group and in 9% and 41% of the MZL group (7% and 19% overall). A total of 3 patients died (1 related to axi-cel, multisystem organ failure during CRS; and 2 unrelated to axi-cel, aortic dissection and coccidioidomycosis infection).
Overall, the median time to the peak level of CAR-T cells (peak median, 38 cells/µL; range, 0-1415) median, was 9 days, and the AUC0–28 was 448 cells/µL × days (range, 6-19,900). In all treated patients with FL, the CAR-T cell peak level was associated with Grade ≥3 CRS (P =.031) and NEs (P =.005).
“Axi-cel had considerable and durable clinical benefit in pts with iNHL, with high ORR and CR rates,” the authors concluded.
Jacobson CA, Chavez JC, Sehgal AR, et al. Primary analysis of ZUMA-5: a phase 2 study of axicabtagene Ciloleucel (Axi-Cel) in patients (pts) with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) [TCT Meetings Abstract 69]. Transplant Cell Ther. 2021;27(3S):S67-S68.