FDA Approves Ponatinib With Chemotherapy for Patients With Newly-Diagnosed Ph-Positive Acute Lymphoblastic Leukemia

On March 19, 2024, the United States Food and Drug Administration (FDA) granted accelerated approval to ponatinib, a tyrosine kinase inhibitor, with chemotherapy for the treatment of patients with newly diagnosed Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL). 

This approval was based on findings from the randomized, active-controlled, multicenter, open-label PhALLCON trial (NCT03589326). This trial included a total of 245 patients with newly diagnosed Ph-positive ALL, who were randomized on a 2 to 1 basis and administered either ponatinib at 30 mg once daily or imatinib at 600 mg once daily with chemotherapy. Chemotherapy included 3 cycles of induction with vincristine and dexamethasone, 6 cycles of consolidation switching between methotrexate and cytarabine, and 11 cycles of maintenance with vincristine and prednisone. It was noted that imatinib plus chemotherapy is an unapproved regimen. Ponatinib was reduced to a dose of 15 mg once daily after patients completed the induction phase and achieved minimal residual disease (MRD)-negative complete remission (CR).

The study authors assessed efficacy based on the MRD-negative CR rate at the end of induction, which was 30% among patients who received ponatinib and chemotherapy compared with 12% among patients who received imatinib and chemotherapy (risk difference 0.18 [95% confidence interval [CI], p-value 0.0004). 

In terms of adverse reactions, hepatic dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias were the most prevalent among these patients. 

The FDA recommends viewing the prescribing information for a description of dosing agents administered with ponatinib.

Source: 

FDA grants accelerated approval to ponatinib with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Published online: March 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-ponatinib-chemotherapy-newly-diagnosed-philadelphia-chromosome