Ponatinib more effective than imatinib for newly diagnosed Ph+ALL leukaemia patients

16 Feb 2023
Ponatinib more effective than imatinib for newly diagnosed Ph+ALL leukaemia patients

“These results provide confirmation that ponatinib plus chemotherapy is an effective, safe treatment option for individuals with Ph+ALL, an aggressive acute leukaemia 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.”– Olatoyosi Odenike, MD, ASCO Expert in Leukemia

In patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL), ponatinib was more effective than imatinib when given with reduced-intensity chemotherapy.

These results were presented at the February 2023 session of the American Society of Clinical Oncology (ASCO) Plenary Series.

The current standard of care for patients with newly diagnosed Ph+ALL includes BCR::ABL1 tyrosine kinase inhibitors (TKIs), among which patients treated with first- or second-generation TKIs often develop resistance.

Additionally, no TKI has been approved in this setting. PhALLCON is the first head-to-head comparison of first-line treatment with ponatinib, a third-generation TKI, compared to imatinib, a first-generation TKI, in combination with chemotherapy in these patients.

In this phase 3 open-label trial, 245 adult patients were randomised 2:1 to receive either ponatinib or imatinib along with reduced-intensity chemotherapy.

At data cutoff, 78 patients (41% ponatinib and 12% imatinib) were still receiving treatment.

The top reasons for discontinuation were hematopoietic stem cell transplantation (30% ponatinib vs 37% imatinib), 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=0.0021).

Event-free survival was reached in imatinib and not in ponatinib, with a trend toward improvement in the experimental arm of the trial.

Adverse events and arterial occlusive events – or a narrowing of the arteries – 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, from 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+ALL.”

Source: ASCO