Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study
- Author(s)
- Chavez, JC; Ujjani, CS; Dickinson, M; Kloos, I; Munoz, J; Ulrickson, ML; Thieblemont, C; Oluwole, OO; Herrera, AF; Lin, Y; Riedell, PA; Kekre, N; de Vos, S; Wulff, J; Williams, CM; Winters, J; Xu, H; Neelapu, SS;
- Details
- Publication Year 2025-05-15,Volume 145,Issue #20,Page 2303-2311
- Journal Title
- Blood
- Publication Type
- Research article
- Abstract
- 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.
- Publisher
- American Society of Hematology
- Keywords
- Humans; Middle Aged; Male; Female; Adult; Follow-Up Studies; *Immunotherapy, Adoptive/methods/adverse effects; *Lymphoma, Large B-Cell, Diffuse/therapy/mortality; Aged; *Antigens, CD19/immunology/therapeutic use; Receptors, Chimeric Antigen; *Biological Products/therapeutic use; Aged, 80 and over; Young Adult; *Tissue Extracts/therapeutic use/adverse effects
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1182/blood.2024027347
- Open Access at Publisher's Site
https://doi.org/10.1182/blood.2024027347- Terms of Use/Rights Notice
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Creation Date: 2025-03-14 07:06:23
Last Modified: 2025-05-27 04:30:41