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

Shah, Bijal D.; Ghobadi, Armin; Oluwole, Olalekan O.; Logan, Aaron C.; Boissel, Nicolas; Cassaday, Ryan D.; Leguay, Thibaut; Bishop, Michael R.; Topp, Max S.; Tzachanis, Dimitrios; O'Dwyer, Kristen M.; Arellano, Martha L.; Lin, Yi; Baer, Maria R.; Schiller, Gary J.; Park, Jae H.; Subklewe, Marion; Abedi, Mehrdad; Minnema, Monique C.; Wierda, William G.; DeAngelo, Daniel J.; Stiff, Patrick; Jeyakumar, Deepa; Dong, Jinghui; Adhikary, Sabina; Zhou, Lang; Schuberth, Petra C.; Faghmous, Imi; Masouleh, Behzad Kharabi und Houot, Roch (2022): 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. In: Journal of Hematology & Oncology, Bd. 15, Nr. 1, 170

Abstract

BackgroundBrexucabtagene 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. MethodsAdults with R/R B-ALL received a single infusion of KTE-X19 (1 x 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. ResultsAfter 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. ConclusionsThese 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch