Impact of Complete Response (CR) on Long-Term Survival Among Patients Receiving Axicabtagene Ciloleucel (axi-cel) for Relapsed or Refractory (r/r) Large B-Cell Lymphoma (LBCL)

Axi-cel is a CD19-directed autologous CAR T-cell therapy approved for the treatment of relapsed/refractory lymphomas. In a 5-year follow-up of ZUMA-1 (Neelapu et al, 2023) 58% of patients (pts) achieved CR, among whom 63% achieved CR by the week-4 assessment. Here, we evaluated the dynamics of achieving CR and its impact on survival in pts with R/R LBCL treated with axi-cel in the real world.Pts who received axi-cel for R/R LBCL in the US between 2017–2020 after ≥ 2 lines of prior therapy and enrolled in the CIBMTR database were analyzed. Pts with other B-cell lymphoma types, in CR at infusion, or missing response/follow-up were excluded. CR was evaluated as a time-to-event endpoint, where relapse/progressive disease (REL/PD) or death were competing risks. Landmark analysis was conducted in pts alive at 6 mo post-infusion. Subsequent overall survival (OS) was estimated for pts in CR (achieved and maintained CR) vs not in CR by 6 mo post-infusion. Progression-free survival (PFS) and REL/PD were estimated for pts in CR by 6 mo. Adjusted analyses identified independent variables as prognostic factors using stepwise selection with a p-value threshold of 0.2 to enter and 0.05 to stay in the model. Adjusted models were fit for CR and for OS following landmark date of 6 mo.Of the 1258 evaluable pts, median age was 62 years (range 53–68; 38% ≥ 65). Histologies included (%): diffuse large B-cell lymphoma (81%), high-grade B-cell lymphoma (16%), and primary mediastinal large B-cell lymphoma (3%). Pts had median 3 lines of prior therapy. Of evaluable pts, 54% would have been ineligible for ZUMA-1, mostly due to comorbidities.With a median follow-up of 24.8 mo, 59% achieved CR post-infusion; 90% of which occurred by 6 mo. Cumulative incidence (95% CI) of CR by 3, 6, and 12 mo post-infusion were 40% (37–43), 54% (51–57), and 58% (56–61), respectively. Baseline variables associated with achieving CR were age ≥ 65 years old (adjusted hazard ratio [HR] 1.48 [95% CI 1.27–1.71]), Eastern Cooperative Oncology Group score < 2 (1.77 [1.09–2.87]), non-bulky disease (1.89 [1.18–3.04]), and prior stem cell transplant (1.35 [1.14–1.60]).A subset of 950 pts alive at 6 mo were analyzed in the landmark analysis. Among them, 514 pts were in CR at 6 mo and 436 pts were not in CR at 6 mo. For pts in CR at 6 mo, post-infusion 2-yr OS, PFS and REL/PD were 84% (81–87), 75% (71–79), and 16% (13–19), respectively. After multivariable adjustment, pts in CR at 6 mo had significantly improved subsequent OS vs pts not in CR (HR 0.22 [0.17–0.28]; adjusted post-infusion 2-yr OS for pts in CR at 6 mo was 84% [81–87] vs pts not in CR at 6 mo, 46% [41–50]).In real-world settings, most responders achieved CR by 6 mo following axi-cel to treat R/R LBCL. Achieving and maintaining CR by 6 mo post-infusion is a potential surrogate for evaluating long-term efficacy at an earlier time-point. Based on these findings, CR should be assessed for potential surrogacy in future clinical trial design.