Ponatinib is a Brc-Abl kinase inhibitor that is especially effective against leukaemias resistant to other protein kinase inhibitors and those with the T315I resistance mutation.1
The pivotal phase II, open-label, single-arm PACE trial evaluated oral ponatinib (45mg once daily) in 449 patients with CML or Ph+ ALL. Patients were eligible for enrolment if they were resistant or intolerant to dasatinib or nilotinib or if they had a confirmed T315I mutation.2
Primary endpoints were major cytogenic response for chronic phase CML and major haematologic response for ALL or acute or blast phase CML.2
Clinically meaningful responses
In the analysis at 12 months (median 14.5 months), there were clinically meaningful responses to ponatinib in all stages of leukaemia.2
Overall, 54% of patients with chronic phase CML and 70% of patients with the T315I mutation achieved a major cytogenetic response. Among patients with advanced CML, 58% of those with accelerated phase disease and 31% of those with blast phase disease acheived a major haematologic response. The Ph+ ALL group showed a major haematologic response rate of 41%.1
The most commonly reported adverse effects were blood dyscrasias (particularly thrombocytopenia) and skin disorders.1
Monitor for pancreatitis
Pancreatitis occurs in around 5% of patients receiving ponatinib; serum lipase should therefore be monitored every 2 weeks for the first 2 months and periodically thereafter. If raised lipase is accompanied by abdominal pain, treatment should be withheld and the patient should be evaluated for pancreatitis.1
- Iclusig Summary of Product of Characteristics, July 2013.
- Cortes JE et al. Oral Presentation at American Society of Hematology Annual Meeting and Exposition, Atlanta, USA, December 2012. Abstract 163.
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