Ponatinib‐review of historical development, current status, and future research

Abstract

AbstractPonatinib is a third‐generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with high potency against Philadelphia chromosome (Ph)‐positive leukemias, including T315I‐mutated disease, which is resistant to first‐ and second‐generation TKIs. Ponatinib was approved for T315I‐mutated chronic myeloid leukemia (CML), CML resistant/intolerant to ≥2 prior TKIs, advanced phase CML and Ph‐positive acute lymphoblastic leukemia (ALL) where no other TKIs are indicated, and T315I‐mutated CML and Ph‐positive ALL. The response‐based dosing of ponatinib in chronic phase CML (CP‐CML) improved treatment tolerance and reduced the risk of toxicities, including cardiovascular risks. Ponatinib‐based therapy also resulted in significantly better outcomes in frontline Ph‐positive ALL compared with prior TKIs and is becoming a new standard of care in this setting. As the clinical development of third‐generation TKIs and their rational combinations progresses, we envision further transformative changes in the treatment of CML and Ph‐positive ALL.