On March 19, 2024, ponatinib (Iclusig) was granted accelerated approval for use with chemotherapy in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL).¹ Ponatinib is a multitargeted kinase inhibitor.

Supporting Efficacy Data and How It Is Used

Approval was based on findings in the open-label PhALLCON trial (ClinicalTrials.gov identifier NCT03589326), in which 245 patients were randomly assigned 2:1 to receive ponatinib at 30 mg once daily (n = 164) or imatinib at 600 mg once daily (n = 81) in combination with 20 cycles of chemotherapy. Chemotherapy consisted of 3 cycles of induction with vincristine and dexamethasone, 6 cycles of consolidation alternating between methotrexate and cytarabine, and 11 cycles of maintenance with vincristine and prednisone. The ponatinib dose was reduced to 15 mg once daily after completion of the induction phase and achievement of undetectable measurable residual disease (MRD) complete remission.

Complete remission after the end of induction was observed in 79% of the ponatinib group vs 63% of the imatinib group. The undetectable MRD complete remission rate at the end of induction was 30% vs 12%, respectively (risk difference = 0.18, P = .0004).

The recommended ponatinib dose is 30 mg once daily with a reduction to 15 mg once daily upon achievement of undetectable MRD complete remission at the end of induction. Ponatinib should be continued with chemotherapy for up to 20 cycles or until loss of response or unacceptable toxicity.

Safety Profile

In PhALLCON, the most common grade 3 or 4 adverse events in the ponatinib group were hepatotoxicity (30% vs 14%), febrile neutropenia (25% vs 20%), pancreatitis/elevated lipase (15% vs 20%), and hypertension (14% vs 7%). The most common grade 3 or 4 laboratory abnormalities were hematologic.

Ponatinib has a boxed warning for arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity. Ponatinib also has warnings/precautions for hypertension, pancreatitis, neuropathy, ocular toxicity, hemorrhage, fluid retention, cardiac arrhythmia, myelosuppression, tumor-lysis syndrome, reversible posterior leukoencephalopathy syndrome, impaired wound healing and gastrointestinal perforation, and embryofetal toxicity. 

REFERENCE

1. Iclusig (ponatinib) tablets, for oral use, prescribing information, Takeda Pharmaceuticals, March 2024. Available at https://www.iclusig.com. Accessed April 1, 2024.