Dr Gesiotto on Optimal Ponatinib Dosing Strategies in CP-CML

The bottom line here is that we can increase the efficacy of [ponatinib] by starting at the higher dose and also decrease the toxicity and dangerous [adverse] effects by decreasing down to 15 mg daily when indicated.

Quinto Gesiotto, MD, a malignant hematologist at Tampa General Hospital, discussed optimal dosing strategies for ponatinib (Iclusig) in the treatment of patients with chronic-phase chronic myeloid leukemia (CP-CML).

Within CML, ponatinib is currently FDA approved for the treatment of adult patients with:

• CP-CML with resistance or intolerance to at least 2 prior TKIs
• Accelerated phase (AP) or blast phase (BP) CML for whom no other TKIs are indicated
• BCR::ABL1 T315I–positive CML in CP, AP, or BP

For patients with CP-CML, the FDA-recommended dose of ponatinib is 45 mg once per day, with reductions to 15 mg once per day once BCR-ABL1 levels fall to 1% or lower. In a pharmacy analysis presented at the 2025 ASH Annual Meeting and Exposition, findings showed that only 13% of patients with CP-CML in the United States were being treated at the 45-mg dose. Among the 213 patients who started ponatinib at a daily dose of 30 mg, only 8% of patients were titrated up to 45 mg once per day; 62% of patients remained at the 30-mg dose, and 28% of patients reduced to 15 mg once per day.

Gesiotto explained that when patients reach the point of requiring treatment with ponatinib, other treatment options have been utilized in prior lines of therapy. For these patients, achieving disease control at this juncture is critical, since treatment options remain limited beyond ponatinib. Given the importance of reaching disease control, starting patients at the 45-mg dose and reducing only when mandated by response criteria allows patients to have the best opportunity to achieve disease control and stay on treatment long term, he explained.

Starting ponatinib at the recommended 45-mg dose gives patients the best chance to respond, Gesiotto continued. Gesiotto added that following the protocol for dose reductions down to 15 mg upon reaching a BCR::ABL1 level of 1% or lower allows for the management of toxicities associated with ponatinib without compromising the chance to drive long-term disease control.