The phase 3 randomized GIMEMA ALL820 trial found frontline treatment with ponatinib plus blinatumomab yielded improved event-free survival (EFS) and response rates compared with imatinib plus chemotherapy for patients with Philadelphia (Ph)–positive acute lymphoblastic leukemia.
Data from the trial, led by Sabina Chiaretti, MD, PhD, of Sapienza University in Rome, Italy, were published in the New England Journal of Medicine.
The study enrolled 236 patients with Ph–positive ALL and randomized 158 to ponatinib plus blinatumomab and 78 to imatinib plus chemotherapy as frontline therapy. The cohort had a median age of 55 years (range, 24-82). Patients in the control group who had persistent disease or measurable residual disease (MRD) reappearance were allowed to crossover to ponatinib plus blinatumomab.
After a median follow-up of 23.7 months, the estimated 24-month EFS rate was 86% in the ponatinib-blinatumomab arm and 67% in the imatinib-chemotherapy arm (P<.001). The rate of EFS with negative MRD was 68% in the ponatinib-blinatumomab arm and 42% in the imatinib-chemotherapy arm. The overall survival rate was 90% in the ponatinib-blinatumomab arm and 85% in the control group.
After induction therapy, 94% of ponatinib-blinatumomab patients and 79% of imatinib-chemotherapy patients achieved a completed hematologic response. After blinatumomab consolidation therapy, 71% of the ponatinib-blinatumomab arm and 49% of the imatinib-chemotherapy arm achieved a molecular response. The cumulative rate of relapse was 5% and 13% for the ponatinib-blinatumomab and imatinib-chemotherapy groups, respectively.
Notably, only 19% of patients in the ponatinib-blinatumomab arm proceeded to receive hematopoietic stem cell transplantation after achieving a first complete hematologic response, the authors reported.
Reference
Chiaretti S, Piciocchi A, Skert C, et al. Ponatinib–Blinatumomab or Imatinib–Chemotherapy for Adult Ph-Positive ALL. New England Journal of Medicine. 2026;395(15):1483-1494. doi:10.1056/nejmoa2606208
Leave feedback about this