Three-year follow-up analysis of first-line axicabtagene ciloleucel in high-risk large B-cell lymphoma (ZUMA-12)

• First-line axi-cel demonstrated an 86% complete response rate and 3-year PFS rate of 75% in efficacy-evaluable patients with high-risk LBCL

• New malignancies and non-relapse mortalities were rare, occurring in 4 patients and 2 patients each, and none were related to axi-cel

ZUMA-12 is a multicenter phase 2 study that evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in patients with high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n=37; 15.9 months median follow-up), axi-cel demonstrated a high rate of complete responses (CR; 78%) and a safety profile consistent with prior experience. Here, we assessed updated outcomes from ZUMA-12 in 40 treated patients after ≥3 years of follow-up. Eligible adults underwent leukapheresis, followed by lymphodepleting chemotherapy and a single axi-cel infusion of 2×106 CAR T cells/kg. Investigator-assessed CR, objective response, survival, safety, and CAR T-cell expansion were assessed. The CR rate among response-evaluable patients (n=37) increased after the primary analysis to 86% (95% CI, 71-95), with a 92% objective response rate. After a median follow-up of 47.0 months (range, 37.1-57.8), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival in response-evaluable patients were 81.8% (63.9-91.4), 73.0% (55.6-84.4), 75.1% (57.5-86.2), and 81.1% (64.4-90.5), respectively. In total, 4 patients had new malignancies, 2 occurring after the data cutoff of the primary analysis, none were related to axi-cel. Eight patients died on study, 2 of whom died from non-relapse mortality causes. After ≥3 years of follow-up, axi-cel demonstrated a high cure rate in first-line high-risk LBCL, with no new safety signals after the primary analysis. Further assessments are needed to determine its benefit versus first-line standard-of-care. This trial was registered at clinicaltrials.gov, as #NCT03761056.