ZUMA-12: Axi-cel shows durable response in LBCL
By Megan Lee
A 3-year follow-up analysis of the ZUMA-12 trial finds that axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, shows high rates of complete and durable responses as part of first-line treatment for patients with high-risk large B-cell lymphoma (LBCL), offering hope for a population with historically modest outcomes.
The findings, led by Julio Chavez (Moffitt Cancer Center, Tampa, Florida, USA) and colleagues, are published in Blood.
The phase 2, multicenter, single-arm, prospective trial assessed axi-cel at a target dose of 2 × 106 CAR T cells/kg in adults with high-risk LBCL, defined as double- or triple-hit lymphomas and/or an International Prognostic Index (IPI) score of ≥3.
After a median follow-up of 47.0 months, 3-year progression-free survival (PFS) was 75.1% and overall survival (OS) was 81.1% in 37 response-evaluable patients. Median PFS, OS, and event-free survival (EFS) were not reached.
Complete response (CR) rates improved to 86%, compared with 78% at the primary analysis, conducted at a median follow-up of 15.9 months.
Notably, 73% of evaluable patients remained in ongoing response, all of whom were in CR. No relapses occurred beyond 18 months post-infusion. “Remissions lasting beyond 2 years may be associated with durability, suggestive of axi-cel as a curative treatment option in the first-line setting,” say the authors.
However, the authors emphasize the relatively small sample size and heterogeneity of the patient population, which may limit the generalizability of these findings. They stress the need for further assessment to evaluate the therapy's broader clinical and economic impact in high-risk LBCL.
Safety outcomes were “consistent with prior experience.” No new safety signals emerged, and non-relapse mortality was rare, occurring in two patients and unrelated to axi-cel. Grade ≥3 adverse events included infections and malignancies unrelated to axi-cel. The therapy demonstrated an acceptable long-term safety profile, with no secondary malignancies of T-cell origin reported.
Further studies are needed to confirm axi-cel's benefit over standard therapies; a phase 3 randomized controlled trial (ZUMA-23) is underway to evaluate its efficacy compared with standard-of-care regimens.
Developed by EPG Health, for Medthority. The article has been developed independently of any sponsor.
