Ponatinib-Blinatumomab or Imatinib-Chemotherapy for Adult Ph-Positive ALL
In brief
Ponatinib-blinatumomab raises 2-year event-free survival to 86% in Philadelphia-positive leukemia
In a randomized phase 3 trial, adults receiving ponatinib plus blinatumomab without frontline chemotherapy had 86% event-free survival at 2 years, compared with 67% on imatinib plus chemotherapy. Responses were also more frequent and relapse less common, but overall survival was 90% versus 85%; follow-up is still short, so longer-term outcomes remain uncertain.
- Journal
- The New England journal of medicine (Q1)
- Published
- 15 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Sabina Chiaretti, Alfonso Piciocchi, Cristina Skert, Matteo Leoncin, Erika Borlenghi, Chiara Cattaneo, et al.
- PMID
- 42874102
- DOI
- 10.1056/NEJMoa2606208
Why clinicians should know about it
- Picked for Hematology (paper of the day, 15 October 2026): Phase 3 trial, chemo‑free ponatinib‑blinatumomab superior
- Picked for Oncology and Radiation Oncology (paper of the day, 15 October 2026): Ponatinib‑blinatumomab vs imatinib‑chemo in Ph‑positive ALL
Abstract
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. 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 ClinicalTrials.gov number, NCT04722848.).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.