Clinical outcomes of chronic myeloid leukemia patients with asciminib provided by a compassionate program in Brazil Open Access

1. Asciminib is an effective option in later lines of CML therapy, particularly in patients with previous intolerance to other TKIs.

2. There was a low rate of cardiovascular events; grade 3 and 4 thrombocytopenia and neutropenia occurred in 26% and 17% respectively.

This study evaluated the clinical outcomes of patients with chronic myeloid leukemia (CML) treated with asciminib, a first-in-class allosteric inhibitor that selectively targets the ABL myristoyl pocket (STAMP) of BCR::ABL1. Through Novartis's Managed Access Program (MAP) in Brazil, asciminib was provided to patients with resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs).

Among 34 patients included, 30 (88.2%) had resistance to prior TKIs and 4 (11.8%) had intolerance; 7 patients carried the T315I mutation. After a median follow-up of 14 months, 35% of the cohort achieved a major molecular response (MMR). Only one patient with the T315I mutation reached MMR. Patients intolerant to previous TKIs responded more favorably than those with resistance (75% vs. 30%; P = 0.07).

The most frequent adverse events were thrombocytopenia (26%) and neutropenia (17%); one patient experienced an acute myocardial infarction. Six patients discontinued treatment, including four due to blast crisis or sepsis (n=2). Two unplanned pregnancies led to temporary treatment interruption, with both patients regaining MMR after reintroduction of asciminib post-delivery. At 32 months, the overall survival rate was 48%. These findings indicate that asciminib is a well-tolerated and effective therapeutic option for patients with CML in later lines of treatment.