KTE-X19 for relapsed/refractory adult B-cell acute lymphoblastic leukemia: phase 2 results from the single-arm, multicenter ZUMA-3 study

By B. Shah, A. Ghobadi, O. Oluwole, A. Logan, N. Boissel, R. Cassaday, T. Leguay, M. Bishop, M. Topp, D. Tzachanis and 21 more. The Lancet, 2021

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Background: We report the pivotal phase 2 results of ZUMA-3, an international, multicenter study evaluating the efficacy and safety of the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy KTE-X19 in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (B-ALL). Methods: Adults with relapsed/refractory B-ALL were enrolled. After leukapheresis and conditioning chemotherapy, patients received a single KTE-X19 infusion (1×106 CAR T cells/kg). The primary endpoint was the overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate by central assessment. ZUMA-3 is registered with ClinicalTrials.gov (NCT02614066). Findings: Among 71 enrolled patients, KTE-X19 was successfully manufactured for 65 and administered to 55. The median age among treated patients was 40 years (IQR, 28–52). At the median follow-up of 16·4 months, 39 patients (70·9% [95% CI, 57–82; p<0·0001]) achieved CR/CRi, with 31 patients (56·4%) achieving CR. The medians for duration of remission, relapse-free survival, and overall survival were 12·8, 11·6, and 18·2 months, respectively. Among patients with CR/CRi, the median overall survival was not reached, and 38 patients (97%) achieved minimal residual disease negativity. Ten patients (18%) received allogeneic stem-cell transplant consolidation post–KTE-X19 infusion. The most common grade ≥3 adverse events were anemia (27 patients [49%]) and pyrexia (20 patients [36%]). Fourteen patients (25%) had grade ≥3 infections. Two grade 5 KTE-X19–related events (brain herniation; septic shock) occurred. Grade ≥3 cytokine release syndrome and neurologic events occurred in 13 (24%) and 14 patients (25%), respectively. Patient-reported outcomes indicated that most evaluable patients experienced improved or stable quality of life. Interpretation: KTE-X19 demonstrated a high CR/CRi rate in relapsed/refractory B-ALL, with the median overall survival not reached in responding patients, and a manageable safety profile. These findings indicate that KTE-X19 has the potential to confer long-term clinical benefit to adult patients with relapsed/refractory B-ALL. Funding: Kite, a Gilead company.

Subfields: Oncology, Pathology and Forensic Medicine, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/0c9386fd1ae24dcbe623339af385df19e260c4d8

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