The Evolving Landscape of Frontline Therapy in Chronic Phase Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by uncontrolled proliferation of mature and maturing granulocytes. The disease is characterized by the presence of translocation t(9;22) leading to the abnormal BCR-ABL fusion. Historically, treatment options included hydroxyurea, busulfan, and interferon-α (IFN-α), with allogeneic stem cell transplant being the only potential curative therapy. More recently, the development of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of CML and turned a once fatal disease into a chronic and manageable disorder. This review aims to discuss the frontline treatment options in chronic-phase CML, provide recommendations for tailoring frontline treatment to the patient, and explore emerging therapies in the field.

The first-generation TKI, imatinib, was FDA approved in 2001 for use in CML. Following the approval and success of imatinib, second- and third-generation TKIs have been developed providing deeper responses, faster responses, and different toxicity profiles. With numerous options available in the frontline setting, choosing the best initial treatment for each individual patient has become a more complex decision. When choosing a frontline therapy for patients with chronic-phase CML, one should consider disease risk, comorbid conditions, and the goal of therapy.