CR at 6 Months Improves 3-Year EFS by Nearly 60% in High-Risk LBCL with Axi-Cel

Results presented at the 2025 ASH Annual Meeting & Exposition suggest that a complete response (CR) at 6 months serves as a strong prognostic indicator for long-term survival in patients with high-risk large B-cell lymphoma (LBCL) receiving frontline axicabtagene ciloleucel (axi-cel). This benefit encompassed better event-free survival (EFS), progression-free survival (PFS), overall survival (OS), and duration of response (DOR).¹

Data showed that, of patients who achieved CR at 6 months compared with 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 hazard ratios, 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 there were moderate to strong correlations found among EFS and PFS with OS at 18 and 36 months.

Axi-cel is an anti-CD19 CAR T-cell therapy that is indicated for patients with relapsed/refractory LBCL. In the multicenter, phase 2 ZUMA-12 trial (NCT03761056), results 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 complete response (CR) was linked with subsequent long-term survival outcomes including EFS, PFS, OS, and DOR in people 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) and 35% of patients were 65 years or older; 32% of patients were female.

More than half of patients had diffuse large B-cell lymphoma 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 patients were mostly stage III/IV (97%). Patients had either activated B-cell (14%) or germinal B-cell (41%) subtype, or other/not tested (46%), 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.

Censored outcomes were assumed to be non-events and were also re-calculated as sensitivity analyses, assuming that censored led to events.

The median follow-up duration was 36.2 months (95% CI, 31.1-36.6) for EFS and PFS, and was 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 coefficient was 0.723 at 6 months (P <.0001), 0.506 at 12 months (P = .0014), and 0.589 at 18 months, 24 months, 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 months, 24 months, and 36 months (all P = .0014).

For OS, the correlation coefficient was 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 coefficient was 0.558 at 6 months P = .0003), 0.420 at 12 months (P = .0097), and 0.506 at 18 months, 24 months, and 36 months (all P = .0014).

Furthermore, EFS and PFS were found to have strong correlations, with at least 0.9 at all timepoints, with correlations for 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 from Athenex, a Gilead company, Janssen medical affairs, Takeda, Fosun Kite, Appia Bio, Galapagos UK, Sellas Life Sciences, Adicet Bio, Kite, Synthekine ImmunoACT, Chimagen Biosciences, ModeX Therapeutics, Bluebird Bio, Sana Biotechnology, Caribou Biosciences, Alimera Sciences, Jazz Pharmaceuticals, CARSgen Therapeutics, Astellas Pharma, Gilead Sciences, Orna Therapeutics, Bristol Myers Squibb, and GlaxoSmithKline; research funding from Kite, a Gilead company, Adicet Bio, Sana Biotechnology, Bristol Myers Squibb, Kite, Alimera Sciences, Cargo Therapeutics, Gilead Sciences; honoraria from MJH Life Sciences, MD Education, and Peerview; 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, Muñoz 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