Subgroup Analysis of the Phase 3 PhALLCON Study of Ponatinib in Ph+ ALL

This is a synopsis of a Peer Exchange series featuring James K. McCloskey, MD, and Lori A. Leslie, MD, of John Theurer Cancer Center, Hackensack University Medical Center.

Shifting to Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), James K. McCloskey, MD, Chief of the Leukemia Division at the John Theurer Cancer Center, discusses results from the phase 3 PhALLCON trial evaluating first-line ponatinib versus imatinib with chemotherapy. Unlike chronic phase chronic myeloid leukemia (CML), Ph+ ALL’s high relapse mortality necessitates maximally effective upfront therapy. Ponatinib’s potency against the emergent gatekeeper mutation T315I has made it an appealing option. However, randomized data was previously lacking.

PhALLCON fulfilled this need, combining ponatinib or imatinib with dose-adjusted chemotherapy backbones tailored to patients’ fitness. Updated results at the 2022 ASH Annual Meeting after a median 20 months of follow-up continue to demonstrate superior responses with ponatinib across all Ph+ ALL subsets. Specifically, major molecular response rates nearly quadrupled with ponatinib versus imatinib in patients over 60 years old, improving from 10% to 40%. This finding is clinically impactful since older patients have the greatest treatment challenges. Benefits were also seen for ponatinib in the P190 BCR-ABL variant and trended positive for the rarer P210 variant.

Encouragingly, safety profiles were comparable between ponatinib and imatinib with no new toxicities, complementing data from the OPTIC trial in CML. As Dr. McCloskey notes, these results continue building the evidence base for ponatinib’s approval in frontline Ph+ ALL. Its combination with blinatumomab is also yielding exciting chemo-free remission durability data. Overall, PhALLCON’s efficacy and safety updates further support ponatinib’s paradigm-changing potential to raise the treatment bar in Ph+ ALL, especially for older patients most in need of improved outcomes.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.