Frontline CP-CML Treatment Selection: Patient Goals and the Role of Asciminib

Patient-specific goals significantly influence treatment selection in the frontline management of chronic-phase chronic myeloid leukemia (CP-CML). Factors such as a patient’s age, comorbidities, treatment tolerability, lifestyle considerations, and long-term goals (e.g., treatment-free remission) must all be taken into account. Shared decision-making is essential to align treatment with patient values, especially when considering potential side effects, pill burden, and monitoring requirements. These individual preferences can impact the choice between established tyrosine kinase inhibitors (TKIs) and newer agents like asciminib.

Asciminib differs from second-generation TKIs in both its mechanism of action and its safety profile. Unlike traditional TKIs that target the ATP-binding site of BCR-ABL1, asciminib is a STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor, offering a novel approach. This unique mechanism allows asciminib to overcome resistance seen with ATP-competitive TKIs and may reduce off-target effects. In clinical trials, asciminib has shown promising efficacy with a more favorable tolerability profile, especially regarding cardiovascular and metabolic side effects, which are often concerns with second-generation TKIs.

Certain CP-CML patients may be especially suited for frontline treatment with asciminib. These include individuals with a history of intolerance or comorbidities that make them poor candidates for second-generation TKIs, such as those at high risk for arterial occlusive events. Patients who prioritize a better side effect profile or who have failed prior TKI therapies may also benefit. As more data become available, asciminib may be increasingly considered for broader use in the frontline setting, particularly where safety and long-term tolerability are top concerns.