Management of Chronic Myeloid Leukemia Patients in Later Lines: The Role of Ponatinib and New Compounds

: Limited therapeutic options and poor response probability still represent some unresolved issue in later lines chronic myeloid leukemia (CML) patients. In addition, sequential treatment is associated with reduced overall survival and may select new mutation, including the T315I, further reducing the therapeutic chances: outside the United States, ponatinib and allogenic stem cell transplant are the only available options. In the last decade, ponatinib improved outcomes in third-line patients, although limited by the risk of severe adverse occlusive events. Dose optimization strategies with lower doses of ponatinib in selected patients have shown to reduce toxicity while retaining efficacy, but higher doses are needed in T315I patients for an adequate disease control. Recently approved by FDA, the first-of-its-kind STAMP inhibitor asciminib has proven safe and effective, obtaining deep and stable molecular responses even in heavily pretreated patients and with T315I mutation. Unfortunately, a significant proportion of patients remain intolerant or refractory, making it crucial to develop new therapeutic options. Among these, novel agents such as vodobatinib and olverembatinib have provided promising result in clinical trials, representing valuable therapeutic possibilities in intolerant or refractory patients. Therefore, a more complex therapeutic paradigm is expected in the near future.