Real-world Italian experience with asciminib in chronic myeloid leukaemia–chronic phase: case series and drug profile overview

Abstract Asciminib selectively targets the myristoyl pocket of ABL1, offering high specificity and a potentially improved safety profile. Its efficacy has been demonstrated in both clinical trials and real-world settings, including heavily pretreated patients and those with T315I mutation. We here report a summary of the drug’s clinical data alongside a real-world case of six adult patients with Philadelphia chromosome–positive chronic myeloid leukaemia (CML) in chronic phase (CP) treated in Italian centres. All patients were resistant or intolerant to at least two prior TKIs and presented with significant comorbidities, predominantly cardiovascular, including hypertension, peripheral arterial disease, ischemic heart disease, and metabolic disorders. Asciminib was administered for a median duration of 16.5 months. All patients achieved or maintained clinically meaningful molecular responses, including major and deep molecular responses. The treatment was well tolerated, with no discontinuations due to adverse events. No arterial occlusive events or significant cardiovascular worsening were observed, nor hematologic toxicity even in a patient with underlying bone marrow hypoplasia. Therefore, in this small real-world cohort of heavily pre-treated CML-CP patients with substantial comorbidity burden, asciminib demonstrated sustained efficacy and a favourable safety profile, particularly regarding cardiovascular tolerability. While the number of patients is small, these findings reinforce the potential role of asciminib for patients with resistance or intolerance to multiple TKIs, as well as for those at high cardiovascular risk, illustrating the relevance of real-world experience in supporting treatment decisions.