FDA Grants Accelerated Approval to Ponatinib Combo in Ph+ ALL

Supporting findings for the approval in this indication came from the phase 3 PhALLCON trial (NCT03589326).

The FDA has granted accelerated approval to ponatinib (Iclusig) in combination with chemotherapy as a treatment for adult patients with newly diagnosed Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).¹

Supporting findings for the approval in this indication came from the phase 3 PhALLCON trial (NCT03589326).

A minimal residual disease (MRD)–negative complete response (CR) was reported in 30% of patients who received ponatinib vs 12% of those who were assigned to receive imatinib (Gleevec; risk difference, 0.18; 95% CI, 0.08-0.28; P = .0004).

Common adverse effects in the trial included hepatic dysfunction, rash, headache, pyrexia, abdominal pain, fatigue, oral mucositis, hypertension, febrile neutropenia, and cardiac arrhythmias.

In the multicenter, open-label PhALLCON trial, 245 adult patients with newly diagnosed Ph-positive ALL were randomly assigned 2:1 to receive ponatinib at 30 mg orally twice a day or imatinib at 600 mg orally once a day plus chemotherapy. Investigators administered 3 cycles of induction therapy with vincristine plus dexamethasone, 6 cycles of consolidation therapy that alternated between methotrexate and cytarabine, and 11 cycles of maintenance therapy with vincristine and prednisone. Patients in the ponatinib arm were able to receive the agent at a reduced dose of 15 mg orally once daily after completing induction chemotherapy and having an MRD-negative CR.

The trial’s primary end point was the rate of MRD-negative CRs at the end of induction therapy.² Secondary end points included event-free survival, molecular responses, overall response rate, time to treatment failure, and overall survival.

According to the FDA, the recommend dose for ponatinib in this indication is 30 mg orally once a day followed by a reduction to 15 mg orally once a day after a patient achieves an MRD-negative CR at the end of induction therapy. Treatment with ponatinib should continue in combination with chemotherapy for a maximum of 20 cycles or until loss of response or unacceptable toxicity.

References

1. FDA grants accelerated approval to ponatinib with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. News release. FDA. March 19, 2024. Accessed March 19, 2024. https://tinyurl.com/mr3nhp26
2. A study of ponatinib versus imatinib in adults with acute lymphoblastic leukemia. ClinicalTrials.gov. Accessed March 19, 2024. https://tinyurl.com/3a67n27v