Management of chronic myeloid leukemia in 2025

Chronic myeloid leukemia (CML) has an annual incidence of approximately two cases per 100,000. The reduction in annual mortality from 10%-20% to 1% with BCR::ABL1 tyrosine kinase inhibitors (TKIs) has resulted in an increased prevalence in the United States of an estimated 150,000 cases in 2025. This translates into a worldwide estimated prevalence of approximately 5 million cases, and hence the need to make TKIs available and affordable to all patients. The four main goals of CML therapy are to (1) improve survival; (2) achieve a durable deep molecular response, which may lead to a treatment-free remission status; (3) reduce short- and long-term side effects; and (4) provide good treatment value. Today, the six approved BCR::ABL1 TKIs, five in frontline therapy (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and all six in later line therapy (including ponatinib), fulfill in one form or another these requirements. Third-generation TKIs that target the ABL1 kinase domain (olverembatinib and ELVN-001) or the myristoyl pocket (TGRX-678 and TERN-701) are under development. Allogeneic hematopoietic stem cell transplantation is a one-time, cost-effective, curative treatment in patients with CML resistant to second-generation TKIs, which is perhaps surprisingly underused in 2025, given the high enthusiasm for it before the development of TKIs. However, serious complications, such as graft-vs-host disease, or death could occur. This review summarizes relevant information concerning the management of CML in 2025, and addresses some CML treatment pathways that became entrenched in the management of CML in the first 15-20 years of TKI experience, which may need to be revisited.