KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study
Mené sur 71 patients atteints d'une leucémie lymphoblastique aiguë à cellules B réfractaire ou récidivante, cet essai de phase II évalue l'efficacité, du point de vue du taux de rémission complète, et la toxicité de KTE-X19, une immunothérapie à base de lymphocytes CAR-T anti CD19
Résumé en anglais
Background : Despite treatment with novel therapies and allogeneic stem-cell transplant (allo-SCT)consolidation, outcomes in adult patients with relapsed or refractory B-precursoracute lymphoblastic leukaemia remain poor, underlining the need for more effectivetherapies.
Methods : We report the pivotal phase 2 results of ZUMA-3, an international, multicentre, single-arm,open-label study evaluating the efficacy and safety of the autologous anti-CD19 chimericantigen receptor (CAR) T-cell therapy KTE-X19 in adult patients with relapsed or refractoryB-precursor acute lymphoblastic leukaemia. Patients were enrolled at 25 sites in theUSA, Canada, and Europe. Eligible patients were aged 18 years or older, with EasternCooperative Oncology Group performance status of 0–1, and morphological disease inthe bone marrow (>5% blasts). After leukapheresis and conditioning chemotherapy, patientsreceived a single KTE-X19 infusion (1 × 106 CAR T cells per kg bodyweight). The primary endpoint was the rate of overall complete remission or complete remission with incomplete haematological recovery by centralassessment. Duration of remission and relapse-free survival, overall survival, minimalresidual disease (MRD) negativity rate, and allo-SCT rate were assessed as secondaryendpoints. Efficacy and safety analyses were done in the treated population (all patientswho received a dose of KTE-X19). This study is registered with ClinicalTrials.gov, NCT02614066.
Findings : Between Oct 1, 2018, and Oct 9, 2019, 71 patients were enrolled and underwent leukapheresis.KTE-X19 was successfully manufactured for 65 (92%) patients and administered to 55(77%). The median age of treated patients was 40 years (IQR 28–52). At the medianfollow-up of 16·4 months (13·8–19·6), 39 patients (71%; 95% CI 57–82, p<0·0001) hadcomplete remission or complete remission with incomplete haematological recovery,with 31 (56%) patients reaching complete remission. Median duration of remission was12·8 months (95% CI 8·7–not estimable), median relapse-free survival was 11·6 months(2·7–15·5), and median overall survival was 18·2 months (15·9–not estimable). Amongresponders, the median overall survival was not reached, and 38 (97%) patients hadMRD negativity. Ten (18%) patients received allo-SCT consolidation after KTE-X19 infusion.The most common adverse events of grade 3 or higher were anaemia (27 [49%] patients)and pyrexia (20 [36%] patients). 14 (25%) patients had infections of grade 3 or higher.Two grade 5 KTE-X19-related events occurred (brain herniation and septic shock). Cytokinerelease syndrome of grade 3 or higher occurred in 13 (24%) patients and neurologicalevents of grade 3 or higher occurred in 14 (25%) patients.
Interpretation : KTE-X19 showed a high rate of complete remission or complete remission with incompletehaematological recovery in adult patients with relapsed or refractory B-precursoracute lymphoblastic leukaemia, with the median overall survival not reached in respondingpatients, and a manageable safety profile. These findings indicate that KTE-X19 hasthe potential to confer long-term clinical benefit to these patients.
