一线 axicabtagene ciloleucel 治疗高危大 B 细胞淋巴瘤的 3 年随访分析：ZUMA-12 研究

ZUMA-12 is a multicenter phase 2 study evaluating axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy as part of first-line treatment for high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n = 37; median follow-up, 15. 9 months), 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, lymphodepleting chemotherapy, and axi-cel infusion (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% confidence interval [CI], 71%-95%), with a 92% objective response rate. After a median follow-up of 47. 0 months (range, 37. 1-57.

8 months), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival 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 axi-cel-related.

Eight patients died on study, 2 of whom died from nonrelapse mortality causes. After long-term follow-up, axi-cel demonstrated a high durable response rate, with no new safety signals after the primary analysis, suggestive of an effective first-line therapy with curative intent in high-risk LBCL.

Further assessments are needed to determine its benefit vs standard of care. This trial was registered at clinicaltrials. gov, as NCT03761056.