Comparison of 2-year outcomes with CAR T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma

Abstract

The SCHOLAR-1 international retrospective study highlighted poor clinical outcomes and survival among patients with refractory large B-cell lymphoma (LBCL) treated with conventional chemotherapy. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated durable responses in patients with refractory LBCL in the pivotal phase 1/2 ZUMA-1 study (NCT02348216). Here, we compared SCHOLAR-1 with the 2-year outcomes of ZUMA-1. Prior to comparison of clinical outcomes, propensity scoring (based on a broad set of prognostic covariates) was used to create balance between ZUMA-1 and SCHOLAR-1 patients. In the pivotal phase 2 portion of ZUMA-1, 101 patients received axi-cel and were evaluable for response and survival. In SCHOLAR-1, 434 and 424 patients were evaluable for response and survival, respectively. ZUMA-1 patients were more heavily pretreated than were SCHOLAR-1 patients. The median follow-up was 27.1 months in ZUMA-1. The objective response rate (ORR) and complete response rate were 83% and 54% in ZUMA-1 vs 34% and 12% in SCHOLAR-1, respectively. The 2-year survival rate was 54% in ZUMA-1 and 20% in SCHOLAR-1, and a 73% reduction in the risk of death was observed in ZUMA-1 vs SCHOLAR-1. These results were consistent with those of an additional standardization analysis in which strata were limited to 2 prognostic factors (refractory categorization and presence/absence of stem cell transplant after refractoriness to chemotherapy) to conserve sample size. Despite the limitations of a nonrandomized analysis, these results indicate that axi-cel produces durable responses and a substantial survival benefit vs non-CAR T-cell salvage regimens for patients with refractory LBCL.

Graphical abstract

Figure 1.

Overview of analysis populations for propensity score–balanced and standardized comparisons. (A) Propensity scores were derived to generate a primary and sensitivity common support data set for ZUMA-1 and SCHOLAR-1, which were then used to estimate the average treatment differences in response to and survival for anti-CD19 CAR T-cell therapy and historical standard of care (non–CAR T-cell therapy). (B) Strata by refractory category and postrefractory SCT for standardization are depicted. Standardized analyses were conducted that equally weighted the proportions of patients by refractory categorization and presence of autologous or allogeneic SCT after establishing refractoriness to salvage therapy (postrefractory SCT) in each study.

Figure 2.

Comparison of confounder-adjusted OS. To control for confounding, the treatment-specific survival functions were obtained using augmented inverse-probability weighted complete-case estimators on the primary common support data set for survival (ZUMA-1, N = 81; SCHOLAR-1, N = 331). mo, month; NE, not estimable.