Initial Findings From the PACE Trial: A Pivotal Phase 2 Study of Ponatinib in Patients With CML and Ph+ ALL Resistant or Intolerant to Dasatinib or Nilotinib, or With the T315I Mutation

摘要

Although the introduction of tyrosine kinase inhibitors (TKIs) has significantly improved outcomes for patients with chronic myeloid leukemia (CML), there are no effective treatments available for patients who fail dasatinib or nilotinib, or for those with the T315I mutation. The new oral pan-BCR-ABL inhibitor ponatinib (AP24534) has demonstrated activity against ABL, other kinases, and the T315I mutation.1 Through its carbon-carbon triple-bond linker, ponatinib avoids the bulky isoleucine residue that constitutes the T315I mutation, instead attaining favorable contact with the residue. Ponatinib has also demonstrated significant activity against all other mutations tested in the laboratory.