Ponatinib in chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia: a guide to its use in the EU

Abstract

Oral ponatinib (Iclusig®) is a novel kinase inhibitor that was designed to overcome resistance mutations in the ABL kinase domain, including T315I. In a phase 2 study, ponatinib therapy was associated with a major cytogenetic response within the first 12 months in >50 % of adults with chronic-phase chronic myeloid leukaemia (CML) and major haematological responses within the first 6 months in ≥50 % of adults with accelerated-phase CML and ≈34 % of adults with blast-phase CML or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL); responses were seen regardless of whether patients were resistant or intolerant to prior dasatinib or nilotinib, or had the T315I mutation. Ponatinib had a manageable tolerability profile; vascular occlusions, cardiac failure and pancreatitis have been reported with ponatinib. Ponatinib is a useful option for adults with chronic-, accelerated- or blast-phase CML or Ph+ ALL who are resistant or intolerant to prior tyrosine kinase inhibitor therapy or who have the T315I mutation.