Ponatinib–Blinatumomab or Imatinib–Chemotherapy for Adult Ph-Positive ALL
Mené sur 236 patients adultes atteints d'une leucémie lymphoblastique aiguë Ph+ (âge médian : 55 ans ; durée médiane de suivi : 23,7 mois), cet essai randomisé évalue l'efficacité, du point de vue de la survie sans événement, et la toxicité de deux traitements de première ligne, l'un combinant ponatinib et blinatumomab, l'autre combinant imatinib et chimiothérapie
Background: The outcome of Philadelphia-positive acute lymphoblastic leukemia (Ph-positive ALL) has greatly improved with the use of tyrosine kinase inhibitors and immunotherapy.
Methods: In this trial, we randomly assigned adult patients with Ph-positive ALL in a 2:1 ratio to receive ponatinib plus blinatumomab (intervention group) or imatinib plus chemotherapy (control group) as frontline treatment. A crossover to the intervention group was allowed for patients with persistence or reappearance of measurable residual disease in the control group. The primary end point was event-free survival.
Research Summary: Ponatinib–Blinatumomab in Adult Ph-Positive ALL
Results: A total of 236 patients underwent randomization: 158 to the intervention group and 78 to the control group. The median age of the patients was 55 years (range, 24 to 82). At a median follow-up of 23.7 months, the estimated 24-month event-free survival was 86% in the intervention group and 67% in the control group (P<0.001). Survival with no measurable residual disease was 68% and 42%, respectively. At the end of induction, a complete hematologic response was observed in 94% of the patients in the intervention group and in 79% of those in the control group. After blinatumomab consolidation, a molecular response was observed in 71% and 49% of the patients, respectively. After crossover to the intervention group, 20 of 31 patients (64%) had a molecular response. Overall survival was 90% in the intervention group and 85% in the control group. The cumulative incidence of relapse was 5% and 13%, respectively. As of this report, only 19% of the patients in the intervention group had undergone hematopoietic stem-cell transplantation after having had a first complete hematologic response.
Conclusions: In this phase 3 trial, a frontline chemotherapy-free targeted and immunotherapeutic approach was superior to the use of imatinib and chemotherapy. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA ALL2820
New England Journal of Medicine , résumé, 2026