Dr Jabbour on the Efficacy of Ponatinib in Newly Diagnosed Ph+ ALL

Elias Jabbour, MD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses efficacy data from the phase 3 PhALLCON trial (NCT03589326) of ponatinib (Iclusig) plus reduced-intensity chemotherapy vs imatinib (Gleevec) plus reduced-intensity chemotherapy in newly diagnosed patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).

Data presented at the 2023 EHA Congress showed that the study met its primary end point, with ponatinib generating a significant improvement in minimal residual disease (MRD)–negative complete remission (CR) rate vs imatinib at the end of induction therapy, which was defined as hematologic CR for at least 4 weeks and MRD negativity of no more than 0.01% of BCR:ABL1 (MR4). The ponatinib regimen (n = 154) elicited a MRD-negative CR rate of 34.4% compared with 16.7% for the imatinib regimen (n = 78; relative risk, 2.06; 95% CI, 1.19-3.56; P = .0021). This end point was unique and not previously used in any phase 3 trials for patients with ALL, Jabbour says.

Regardless of CR assessment, 41.6% of patients in the ponatinib arm achieved MRD negativity at the end of induction vs 20.5% of patients in the imatinib arm (relative risk, 1.94; 95% CI,1.19-3.17; P = .0017).

The trial enrolled adult patients with newly diagnosed Ph-positive ALL or BCR:ABL1-positive ALL without a history or current diagnosis of chronic myeloid leukemia. Patients were randomly assigned in a 2:1 fashion to receive ponatinib at 30 mg once daily, with dose reduction to 15 mg once daily, in combination with reduced intensity chemotherapy, or imatinib at 600 mg once daily with reduced-intensity chemotherapy. Chemotherapy was comprised of vincristine and dexamethasone for 3 cycles during induction, methotrexate and cytarabine for 6 cycles during consolidation, and with vincristine and prednisone for 11 cycles during maintenance. All cycles lasted 28 days. Ponatinib or imatinib were continued as single agents following maintenance.