Ponatinib- vs Dasatinib-Based Induction in Adults With Newly Diagnosed Ph+ ALL

BACKGROUND

Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) outcomes have improved signifi cantly with the incorporation of BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs). Reduced-intensity chemotherapy backbones with potent TKIs are now a preferred treatment approach, particularly for older patients or those with comorbidities. Achieving early, deep molecular responses has emerged as a critical predictor of long-term outcomes and a potential surrogate end point for therapeutic efficacy. Induction with ponatinib plus reduced-intensity chemotherapy has demonstrated high rates of minimal residual disease (MRD)–negative complete remission (CR) (Jabbour et al). However, direct comparative data between ponatinib and second-generation TKIs in the induction setting remain limited.

MATERIAL AND METHODS

This was a retrospective study of newly diagnosed adult patients with Ph+ ALL who received ponatinib- or dasatinib-based induction regimens between September 2019 and November 2025. The study objective included rates of CR at the end of induction, including MRD and molecular MRD negativity. MRD negativity was defi ned as achieving less than 0.01% leukemic cells of total nucleated cell by flow cytometry and/or polymerase chain reaction. Secondary objectives included relapse rates, allogeneic transplant (HCT) in CR1, and safety.

RESULTS

A total of 91 adult patients were included; 50 received ponatinib, and 41 received dasatinib. Median age was 52 years (range, 25-84), with 25% of patients aged 65 years or older. Most patients received 1 cycle of induction therapy (76% with ponatinib and 51% with dasatinib). Median white blood cell at diagnosis was 75 x 109/L in the ponatinib group and 55 x 109/L in the dasatinib group. CR was achieved in 100% of patients receiving ponatinib-based induction, compared with 90% in the dasatinib group. Molecular MRD negativity rates were 38% with ponatinib and 30% with dasatinib, while flow cytometry MRD negativity rates were 60% and 56%, respectively. Among responders, 40% of patientstreated with ponatinib and 68% treated with dasatinib proceeded to allogeneic HCT in CR1.

CONCLUSION

Early results demonstrate that ponatinib-based induction was associated with high rates of CR and molecular response compared with dasatinib. These fi ndings suggest ponatinib may facilitate deeper early responses and could reduce the need for allogeneic HCT in select patients.