Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study
Bijal Shah, Armin Ghobadi, Olalekan O. Oluwole, Aaron C. Logan, Nicolas Boissel, Ryan D. Cassaday, Thibaut Leguay, Michael R. Bishop, Max S. Topp, Dimitrios Tzachanis, Kristen M. O’Dwyer, Martha Arellano, Yi Lin, Maria R. Baer, Gary J. Schiller, Jae H. Park, Marion Subklewe, Mehrdad Abedi, Monique C. Minnema, William G. Wierda, Daniel J. DeAngelo, Patrick J. Stiff, Deepa Jeyakumar, Jinghui Dong, Sabina Adhikary, Lang Zhou, Petra Schuberth, Imi Faghmous, Behzad Kharabi Masouleh, Roch Houot
Abstract
Abstract Background Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care. Methods Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 10 6 CAR T cells/kg). Long-term post hoc subgroup assessments of ZUMA-3 were conducted. Outcomes from matched patients between historical clinical trials and ZUMA-3 patients were assessed in the retrospective historical control study SCHOLAR-3. Results After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients ( N = 55) in phase 2 was 71% (56% CR rate); medians for duration of remission and overall survival (OS) were 14.6 and 25.4 months, respectively. Most patients responded to KTE-X19 regardless of age or baseline bone marrow blast percentage, but less so in patients with > 75% blasts. No new safety signals were observed. Similar outcomes were observed in a pooled analysis of phase 1 and 2 patients ( N = 78). In SCHOLAR-3, the median OS for treated patients from ZUMA-3 ( N = 49) and matched historical controls ( N = 40) was 25.4 and 5.5 months, respectively. Conclusions These data, representing the longest follow-up of CAR T-cell therapy in a multicenter study of adult R/R B-ALL, suggest that KTE-X19 provides a clinically meaningful survival benefit with manageable toxicity in this population. Trial Registration : NCT02614066.