A 6 y o boy with Ph+ ALL relapsed with a T315I mutation. Does anyone know the adequate ponatinib dosage for this patient?

Dear Dr. Abecasis,

You ask for the dose of Ponatinib in a 6-year old child.
Assuming that the body surface of an adult is on average 1.73 sqm, the starting dose for a child would be 25 mg/sqm. However, I'm not aware of a formal trial having tried to collect data on any dosage in children with T315 I mutation. So this approach would be a compassionate use in your responsibility as treating physician as the safety and efficacy of Ponatinib (Iclusig, TM) in patients less than 18 years of age have not been established.

Ponatinib is indicated for adult patients with chronic, accelerated, or blast phase T315I-positive chronic myeloid leukemia (CML) for whom no other TKI therapy is indicated. Note: Not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase CML.

The optimal dose in adults is not identified. In adults the dose is 45 mg PO qDay initially; continue as long as there is no evidence of disease progression or unacceptable toxicity. Coadministration with strong CYP3A inhibitors: Reduce dose to 30 mg qDay in adults. In clinical trials on adult patients , the starting dose was 45 mg PO once daily; however, 59% of the adult patients required dose reductions to 30 mg or 15 mg once daily. Consider reducing the dose in patients who have achieved a major cytogenetic response.
Consider discontinuing if response has not occurred by 3 months.

Also it might be prudent to ask for further information from the supplier:
ARIAD Pharmaceuticals, Inc; 26 Landsdowne Street; Cambridge, MA 02339-4234

With kind regards and all the best wishes for the child Meinolf Suttorp

Meinolf is right about no data in pediatrics. Phase 1 in pediatric population has not been done yet. There is only one case report in the literature about pediatric experience (Pediatr Blood Cancer. 2015 Nov;62(11):2050-1). They used 45 mg daily for an adolescent >70kg but reduced it to 15 mg for a concern of side effects.

We have used it for a 9 yo with Ph+ ALL and T315I mutation. This weight is about 30 kg and 1 m² BSA. The patient received 15 mg daily and had a great response. I also hear from my US colleagues about their experience with children.

Nobuko Hijiya