Journal of Hematology & Oncology (Dec 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

  • Bijal D. 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 L. 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 Stiff,
  • Deepa Jeyakumar,
  • Jinghui Dong,
  • Sabina Adhikary,
  • Lang Zhou,
  • Petra C. Schuberth,
  • Imi Faghmous,
  • Behzad Kharabi Masouleh,
  • Roch Houot

DOI
https://doi.org/10.1186/s13045-022-01379-0
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 11

Abstract

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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 × 106 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.

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