Introduction to a series of reflections on a quarter century of TKIs for CML

Abstract

This Review Series highlights the transformative impact of tyrosine kinase inhibitors (TKIs) on therapy for chronic myeloid leukemia (CML) in the last 25 years. Brian J. Druker introduces the series by providing a Perspective that recalls the initial presentation at the 1999 American Society of Hematology annual meeting, revealing a 100% response rate at effective doses of imatinib in the phase 1 study. Guilhot and Hehlmann review long-term outcomes of patients with CML treated with TKIs in major studies and note that survival of patients with CML now approaches that of the general population. Hughes et al address the issue of treatment-free remission and explore the criteria for safely discontinuing TKIs for select patients. Finally, Cruz-Rodriguez and Deininger discuss mechanisms of resistance, emerging therapeutic strategies, and the promise of BCR::ABL1 degraders and TKI combinations.