Ibrahim Aldoss, MD, City of Hope, Duarte, California, discusses a post hoc analysis of the phase 3 PhALLCON trial which compared ponatinib vs imatinib for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who did not reach minimal residual disease (MRD) negativity by end of induction.

The results of this analysis demonstrated superior efficacy and durability for ponatinib than imatinib, and, Dr Aldoss stated, “These results support the clinical benefit and tolerability of continuing ponatinib beyond cycle 3 in patients with newly diagnosed Ph+ ALL who have not achieved MRD negativity by the end of induction.”

Transcript:

I am Dr Ibrahim Aldoss from City of Hope, Division of Leukemia, Department of Hematology and STEM cell Transplant.

Ponatinib is a third generation TKI approved for frontline treatment of adult patients with Ph+ ALL in combination with chemotherapy. This approval is based on the phase 3 international PhALLCON study that randomized newly diagnosed adult patients with Ph+ ALL in 2:1 fashion to either ponatinib and low intensity chemotherapy or imatinib and low intensity chemotherapy. The primary endpoint in the PhALLCON study was MRD negative CR at the end of induction, and the study met the primary endpoint and ponatinib was associated with superior MRD negative CR at the end of induction compared to imatinib.

Now here in this ASCO abstract presentation, we did a post-hoc analysis from the PhALLCON study focused on patients who did not achieve MRD negative CR at the end of induction, but they remain on the therapy. The analysis evaluated baseline characteristics, molecular response, event-free survival and safety profile among patients who receive either ponatinib or imatinib.

Among 232 patients who were centrally confirmed BCR-ABL1, 140 patients did not achieve MRD negativity by the end of induction. Of this patient, 113 patients continued treatment after end of induction. By the end of the treatment, both end of induction MRD negativity was higher in patients received ponatinib compared to imatinib and the same thing, both end of induction molecular response. MR4.5 was higher in the ponatinib arm compared to imatinib. The percentages were 37% versus 10%. Event-free survival and overall survival in patients who didn't reach MRD negativity by the end of induction was superior in patients who received ponatinib compared to imatinib with 2-year event-free survival of 87% in patients who received ponatinib compared to 62% in patients receiving imatinib. Similarly, PFS was superior in the ponatinib arm compared to imatinib arm, 2-year PFS was 36% in the ponatinib arm compared to 13% in the imatinib arm.

Safety profile was comparable with similar rates of treatment-emergent adverse events in patients who continued ponatinib and imatinib. Treatment-emergent arterial occlusive events were rare overall, and rates were not significantly different between the 2 arms.

In conclusion, patients who didn't achieve MRD negativity by the end of induction and continued treatment beyond cycle 3 had higher rates of deep molecular response after end of induction with ponatinib plus chemotherapy compared to imatinib and chemotherapy. Rates of treatment-emergent adverse events including arterial occlusive events were similar between the ponatinib and imatinib groups. These results support the clinical benefit and tolerability of continuing ponatinib beyond cycle 3 in patients with newly diagnosed Ph+ ALL who have not achieved MRD negativity by the end of induction. Thank you.

Source:

Aldoss I, Cheng Y, et al. A phase II study of asandeutertinib (TY-9591) in advanced NSCLC patients with EGFR-positive mutations and brain metastases. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 6510.