SOHO State of the Art Updates and Next Questions: Combination Therapy in Chronic Myeloid Leukemia in Chronic Phase.

Therapeutic strategies for chronic myeloid leukemia (CML) are rapidly evolving, with novel agents emerging to address the limitations of current treatments. Goals of CML management are disease control and achieve a deep and sustained molecular response for a possible successful treatment-free remission (TFR). However, a significant proportion of patients fail to reach adequate molecular response and require sequential therapies. A crucial aspect of treatment resistance lies in the persistence of leukemic stem cells (LSCs), which serve as a reservoir for disease recurrence. Increasing focus is placed on combination strategies to overcome the constraints of TKI monotherapy. Various strategies have been explored, starting with the combination of interferon (IFN) and TKIs. The investigation of alternative administration methods, dosing regimens, or extended treatment durations in clinical trials involving IFN represents potential avenues to address current conflicting results. Additionally, the combination of ATP-competitive TKIs with asciminib has shown encouraging preclinical and clinical results, with further data needed for a comprehensive safety profile. Recently, efforts to inhibit other signaling pathways have been explored but with contrasting results. Despite ongoing advancements, TKIs remain the cornerstone of both current and future combination therapies. Their integration with personalized approaches is crucial to overcome complex biological challenges and ensure long-term, effective and safe treatment for CML patients.