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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)
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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)

Sattva S. Neelapu, Frederick L. Locke, Nancy L. Bartlett, Lazaros J. Lekakis, Patrick M. Reagan, David B. Miklos, Caron A. Jacobson, Ira Braunschweig, Olalekan O. Oluwole, Tanya Siddiqi, …
Biology of blood and marrow transplantation, Vol.26(3), pp.S232-S232
03/2020
DOI: 10.1016/j.bbmt.2019.12.474
url
https://doi.org/10.1016/j.bbmt.2019.12.474View
Published (Version of record) Open Access

Abstract

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. 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. 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 < .0001 for both ORR and CR rate). The standardized 2-year survival rate was 50% (95% CI, 40-59) in ZUMA-1 and 12% (95% CI, 9-15) in SCHOLAR-1, yielding a 73% reduction in the risk of death (HR, 0.27; P < .0001). 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.

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