A Comparison of 2-Year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel [Axi-Cel]) and SCHOLAR-1 in Patients (Pts) with Refractory Large B Cell Lymphoma (LBCL)

Background In the SCHOLAR-1 retrospective analysis of pts with refractory LBCL, the objective response rate (ORR) was 26% and the complete response (CR) rate was 7% with available salvage therapies in the pre-chimeric antigen receptor (CAR) T cell therapy era (Crump M, et al. Blood. 2017). These results served as a benchmark for novel therapies. ZUMA-1 (NCT02348216) is the pivotal Phase 1/2 study evaluating axi-cel, an autologous anti-CD19 CAR T cell therapy, in refractory LBCL. At a median follow-up of 27.1 mo, the ORR in ZUMA-1 was 83% and the CR rate was 58% (Locke FL, et al. Lancet Oncol. 2019). Here, we describe comparative analyses of outcomes in ZUMA-1 and SCHOLAR-1 after adjusting for refractory status. Methods Pts in both studies had refractory LBCL defined as stable disease of ≤ 6 mo with ≥ 4 cycles of frontline or ≥ 2 cycles of later-line therapy, progressive disease as best response, or relapse ≤ 12 mo post-autologous stem cell transplant (SCT). To address potential imbalances between studies, standardized analyses were performed that equally weighted the proportions of pts by refractory categorization (primary refractory, refractory to ≥ 2nd-line therapy, or relapse after SCT) and presence of post-refractory SCT in each study. Stratified Cochran-Mantel-Haenszel (CMH) tests and Cox models were used to compare the odds ratio (OR) for response and hazard ratio (HR) for survival between ZUMA-1 and SCHOLAR-1. P values were not adjusted for multiplicity. Results In Phase 2 of ZUMA-1, 101 pts received axi-cel. In SCHOLAR-1, 508 and 497 pts were evaluable for response and survival, respectively. The median follow-up in ZUMA-1 was 2.3 y, and the median follow-up from the overall SCHOLAR-1 study ranged from 7.6-14.8 y across different cohorts. Compared with SCHOLAR-1, ZUMA-1 had higher proportions of pts who received ≥ 3 lines of therapy (69% vs 23%) and pts refractory to 2nd- or later-line therapy (76% vs 62%). Fewer pts in ZUMA-1 were classified as primary refractory vs those in SCHOLAR-1 (26% vs 45%), and relapse rates within 1 y of SCT were similar between studies (21% vs 18%). The standardized ORR and CR rate in ZUMA-1 vs SCHOLAR-1 were 72% and 54% vs 22% and 7%, respectively. The OR for ORR and CR rate were 7.2-fold and 11.5-fold higher, respectively in ZUMA-1 vs SCHOLAR-1 (CMH test; P Conclusions This standardized analysis of ZUMA-1 and SCHOLAR-1 indicates that treatment with axi-cel in this selected population increased odds of CR and reduced the risk of death versus standard salvage regimens in an unselected population. Although limited by retrospective evaluation and cross-study comparisons, these results support axi-cel as a highly effective treatment option for pts with refractory LBCL.