Frontline Axi-Cel CR Linked With Improved Survival in High-Risk LBCL

Patients with high-risk large B-cell lymphoma (LBCL) treated with frontline axicabtagene ciloleucel (axi-cel; Yescarta) who achieved a complete response (CR) at 6 months were more likely to have subsequent long-term survival benefit, including event-free survival (EFS), progression-free survival (PFS), overall survival (OS), and duration of response (DOR), according to results presented during the 2025 American Society of Hematology Annual Meeting and Exposition.¹

Of patients who achieved CR at 6 months vs those who did not, the 3-year Kaplan-Meier estimates for EFS were 88.9% vs 30.0%, respectively. These rates were 88.9% vs 33.8% for PFS, 92.6% vs 50.0% for OS, and 88.9% vs 50.0% for DOR, respectively. Additionally, patients in CR at 6 months had improved long-term outcomes, according to lower Cox regression–adjusted HRs, which were all P <.05, except for DOR (P = .063).

“Adjusted risk of progression, mortality, and shorter CR duration were at least 10 times greater for 6-month survivors not in CR,” lead study author Sattva S. Neelapu, MD, a professor of the Department of Lymphoma and Myeloma of The University of Texas MD Anderson Cancer Center in Houston, said in a poster presentation recorded for the meeting. “CR at 6 months has potential to serve as a surrogate end point for long-term outcomes in future clinical trials evaluating axi-cel as part of first-line high-risk LBCL treatment.”

Neelapu added that moderate to strong correlations were found among EFS, PFS, and OS at 18 and 36 months.

Axi-cel is an anti-CD19 chimeric antigen receptor T-cell therapy indicated for patients with relapsed/refractory LBCL. Results from the multicenter, phase 2 ZUMA-12 trial (NCT03761056) showed that the CR rate in response-evaluable patients (n = 37) went from 78% in the primary analysis, which had a median follow-up of 16 months, to 86% at 3 years (95% CI, 71%-95%) with a 3-year PFS rate of 75%.²

In this ZUMA-12 analysis, investigators sought to evaluate whether a 6-month CR was linked with subsequent long-term survival outcomes, including EFS, PFS, OS, and DOR in patients with high-risk LBCL following frontline axi-cel. ¹

Patient Response Rates and Characteristics

Thirty-seven patients were included in the response-evaluable analysis, 27 of whom were in CR at 6 months. In the overall group, the median age was 61 years (range, 56-70); 35% of patients were 65 years and older; 32% of patients were women.

More than half of patients had diffuse LBCL at initial diagnosis (57%) and an ECOG performance status of 1 (59%). Eighty-four percent of patients had an International Prognostic Index total score of 3 or higher, and 97% of patients had stage III/IV disease. Patients had an activated B-cell (14%) or a germinal B-cell (41%) subtype; 46% were other/not tested, and 64% had neither double-hit nor triple-hit lymphoma at diagnosis.

The best response to prior therapy was partial response (53%), stable disease (6%), or progressive disease (42%). In total, 64%, 46%, and 51% of patients had alterations/overexpression in BCL-2, BCL-6, and C-MYC, respectively.

There were no significant differences in baseline characteristics between the CR status groups.

In the primary analysis, censored outcomes were assumed to be nonevents. According to the study authors, “Sensitivity analyses were repeated under the opposite assumption of events.”

The median follow-up duration was 36.2 months (95% CI, 31.1-36.6) for EFS and PFS, and 38.1 months (95% CI, 36.5-42.0) and 35.2 months (95% CI, 30.2-35.7) for OS and DOR, respectively.

Additional Efficacy End Points

Additional efficacy data looked at Pearson correlations of CR status at 6 months, as well as long-term outcomes at 6, 12, 18, 24, and 36 months. For EFS, the correlation coefficients were 0.723 at 6 months (P < .0001), 0.506 at 12 months (P = .0014), and 0.589 at 18, 24, and 36 months (all P = .0001). For PFS, the correlation coefficient was 0.650 at 6 months (P < .0001), 0.420 at 12 months (P = .0097), and 0.506 at 18, 24, and 36 months (all P = .0014).

For OS, the correlation coefficients were 0.274 at 6 months (P = .101), 0.265 at 12 months (P = .1128), 0.472 at 18 months (P = .0032), 0.558 at 24 months (P = .0003), and 0.483 at 36 months (P = .0025). Finally, for DOR, the correlation coefficients were 0.558 at 6 months (P = .0003), 0.420 at 12 months (P = .0097), and 0.506 at 18, 24, and 36 months (all P = .0014).

Furthermore, EFS and PFS were found to have strong correlations, with at least 0.9 at all time points, with correlations between these respective end points and OS ranging from 0.65 to 0.85 between 18 months and 36 months (all P < .05). These data were similar when assuming the censored observations were events, Neelapu added.

Disclosures: Neelapu cited consultancy and expert testimony for Adicet Bio, Alimera Sciences, Appia Bio, Astellas Pharma, Athenex (a Gilead company), Bluebird Bio, Bristol Myers Squibb, CARSgen Therapeutics, Caribou Biosciences, Chimagen Biosciences, Fosun Kite, Galapagos UK, Gilead Sciences, GSK, Janssen, Jazz Pharmaceuticals, Kite, ModeX Therapeutics, Orna Therapeutics, Sana Biotechnology, Sellas Life Sciences, Synthekine ImmunoACT, and Takeda; research funding from Adicet Bio, Alimera Sciences, Bristol Myers Squibb, Cargo Therapeutics, Gilead Sciences, Kite, Sana Biotechnology; honoraria from MD Education, MJH Life Sciences, and Peerview. Neelapu is a current equity holder in and of stock options in Longbow Immunotherapy.

Reference

1. Neelapu SS, Fridman M, Ray M, et al. Surrogate endpoints as prognostic factors for long-term outcomes among patients receiving axicabtagene ciloleucel in frontline high-risk large B cell lymphoma. Blood. 2025;146(supplement 3):3717. doi:10.1182/blood-2025-3717
2. Chavez JC, Dickinson M, Munoz J, et al. Three-year follow-up analysis of first-line axicabtagene ciloleucel for high-risk large B-cell lymphoma: the ZUMA-12 study. Blood. 2025;145(20):2303-2311. doi:10.1182/blood.2024027347