Ponatinib May Be More Effective Than Imatinib for Newly Diagnosed Patients With Ph-Positive ALL

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In newly diagnosed patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL), ponatinib was more effective than imatinib when given with reduced-intensity chemotherapy. These results were presented by Jabbour et al during the February ASCO Plenary Series session (Abstract 398868).

The current standard of care for newly diagnosed patients with Ph-positive ALL includes BCR::ABL1 tyrosine kinase inhibitors (TKIs), and patients treated with first- or second-generation TKIs often develop resistance. Additionally, no TKI has been approved in this setting. The PhALLCON trial is the first head-to-head comparison of first-line treatment with ponatinib (a third-generation TKI) vs imatinib (a first-generation TKI) in combination with chemotherapy in these patients.

PhALLCON Details

In this phase III open-label trial, 245 adult patients were randomly assigned 2:1 to receive either ponatinib or imatinib along with reduced-intensity chemotherapy. At data cutoff, 78 patients (41% in the ponatinib group and 12% in the imatinib group) were still receiving treatment. The top reasons for treatment discontinuation were hematopoietic stem cell transplantation (30% in the ponatinib group vs 37% in the imatinib group), adverse events (12% vs 12%), and lack of efficacy (7% vs 26%).

The primary endpoint of measurable residual disease negativity complete remission—or no detectable amount of disease—after a 12-week induction period was significantly higher in the ponatinib group compared to the imatinib group (34.4% vs 16.7%, P = .0021). Event-free survival was reached in the imatinib group and not in the ponatinib group, with a trend toward improvement in the experimental arm of the trial. Adverse events and arterial occlusive events were similar between the treatment groups.

“The potential benefit to patients who achieve this early, deep response may be important to improve long-term survival outcomes,” said lead author Elias Jabbour, MD, of The University of Texas MD Anderson Cancer Center. “The trial results indicate ponatinib as a potential standard of care for patients newly diagnosed with Ph-positive ALL.”

ASCO Expert Perspective

“These results provide confirmation that ponatinib plus chemotherapy is an effective, safe treatment option for individuals with Ph-positive ALL, an aggressive acute leukemia with a historically poor outcome. Future research comparing ponatinib to a second-generation TKI would help determine the best choice of TKI for these patients. Chemotherapy-free regimens incorporating TKIs in combination with antibody-based therapies are being actively investigated in this disease,” said Olatoyosi Odenike, MD, of UChicago Medicine, and an ASCO Expert in leukemia.

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