Ponatinib Shows Efficacy in the Treatment of Leukemia Patients

Some patients with BCR-ABL mutations, especially those with the T315I mutation, still develop resistance even after treatment with first-generation and second-generation TKIs. Prior to the approval of ponatinib, the third-generation TKI, no TKIs were available to overcome the resistance, refractoriness or intolerance in these patients with BCR-ABL mutations.

In the phase II clinical study of ponatinib, a total of 449 patients with CML or Ph+ ALL (including 267 patients with chronic-phase CML) were enrolled. The trial data showed that among patients with chronic-phase CML, the overall major cytogenetic response rate was 56% (with response rates of 51% and 70% in patients without and with the T315I mutation, respectively), and the overall major molecular response rate was 34% (with response rates of 27% and 56% in patients without and with the T315I mutation, respectively). In patients with accelerated-phase CML, blast-phase CML and Ph+ ALL, the major hematologic response rates achieved with ponatinib were 55%, 31% and 41%, respectively.

Therefore, as a highly potent oral TKI, ponatinib represents a crucial clinical option for patients with refractory CML, particularly those harboring the T315I mutation. Ponatinib targets a specific mutation in CML cells known as T315I, which renders these cells resistant to currently approved TKIs. It can block certain proteins that promote cancer cell growth. Administered once daily, ponatinib is indicated for the treatment of patients with chronic, accelerated, and blast-phase CML and Ph+ ALL whose leukemias are resistant or intolerant to a class of drugs called tyrosine kinase inhibitors (TKIs).

The most common non-hematologic adverse reactions (≥20%) of ponatinib include hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions include thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia.