The Food and Drug Administration (FDA) has granted an accelerated approval to Iclusig (ponatinib) with chemotherapy for the treatment of adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the agency has announced.
The approval was based on the findings of the PhALLCON trial of 245 patients with newly diagnosed Ph+ ALL who received either 30 milligrams of Iclusig orally daily or 600 milligrams of Gleevec (imatinib) orally daily plus chemotherapy. The Iclusig dose was reduced to 15 milligrams daily following the induction phase of chemotherapy and achievement of minimal residual disease (MRD)-negative (the absence of detectable malignant cells) complete remission (CR; no signs or symptoms of cancer).
The MRD-negative CR rate at the end of induction was 30% in the Iclusig arm and 12% in the Gleevec arm, according to the agency.
“This study has established [Iclusig] as the standard of care for Ph-positive ALL,” said Dr. Elias Jabbour, a professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, during the presentation of the PhALLCON findings at the 2023 School of Hematologic Oncology Annual Meeting. “It is superior to [Gleevec] in inducing a higher rate of MRD negativity at 12 weeks. This superiority was associated with a better PFS and improvement the long-term EFS. [Although] we see an advantage in efficacy, we did not see an increase in AEs. Therefore, based on these data, we hope that Iclusig will be approved.”
The most common side effects, according to the FDA’s announcement, were liver dysfunction, joint pain, rash and related conditions, headache, fever, 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.
The FDA reported that the recommended Iclusig dose is 30 milligrams orally daily with a reduction to 15 milligrams orally daily after achieving MRD-negative CR at the end of induction, and patients can continue Iclusig with chemotherapy for up to 20 cycles until loss of response or unacceptable toxicity.
The FDA previously approved a supplemental new drug application for Iclusig for patients with chronic-phase chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors in 2020.
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