Continuing Ponatinib Benefits Patients Without Early MRD Negativity in Ph+ ALL

The phase 3 PhALLCON trial (NCT03589326) initially showed that ponatinib (Iclusig) led to significantly higher rates of measurable residual disease (MRD) negativity with complete remission compared to imatinib (Gleevec) in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This primary end point, achieved at the end of induction, established ponatinib's superior efficacy with comparable safety.

An abstract at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting presents a post hoc analysis focusing on patients who did not achieve MRD negativity by the end of induction. Among 232 patients, 140 (56% on ponatinib, 69% on imatinib) did not reach MRD negativity by the end of induction Of these, 113 continued treatment, and notably, 48 patients (35 on ponatinib, 13 on imatinib) later achieved MRD negativity after cycle 4 day 1. The median duration of MRD negativity was not reached for patients on ponatinib, indicating a durable response, while it was 3.8 months for patients on imatinib.

Even in the group that did not achieve early MRD negativity, the 2-year event-free survival (EFS) was better with ponatinib (82%) compared with imatinib (62%). For the 48 patients who achieved MRD negativity later, 2-year EFS remained high for both ponatinib (88%) and imatinib (80%). While adverse event rates were high in both groups, dose modifications due to side effects were more frequent with ponatinib (71%) than imatinib (54%).

These findings suggest that for patients with Ph+ ALL who do not achieve MRD negativity by the end of induction, continuing ponatinib treatment offers significant clinical benefit, leading to deeper and more durable molecular responses and improved event-free survival compared with imatinib. This supports the ongoing use of ponatinib in patients who do not achieve early MRD negativity.

In an interview with Targeted Oncology, Ibrahim Aldoss, MD, hematologist-oncologist at City of Hope and investigator on this post hoc analysis, described the study and its findings.