DP124 | CHARACTERISTICS, OUTCOMES AND MUTATIONAL ANALYSIS OF CHRONIC MYELOID LEUKEMIA PATIENTS RECEIVING ASCIMINIB IN BOLOGNA

Asciminib (asc), an allosteric inhibitor, is an effective and safe option for patients (pts) in late and early chronic-phase chronic myeloid leukemia (CML). In Italy, outside of clinical trials, in April 2019 asc became available through a Managed Access Program approved by Novartis for pts resistant or intolerant (R/I) to ≥2 tyrosine-kinase inhibitors (TKIs) without T315I mutation; since August 2024 it has been approved for commercial use by AIFA. We report our single-center experience of asc use as per clinical practice. We retrospectively collected data of 21 CML pts treated with asc in our Institute between November 2020 and November 2024. Most pts were elderly with a median age of 71 (range 37-90) years and with multiple comorbidities (57% had CCI >4), including cardiovascular ones (86%). The median number of prior TKIs were 3 (2-4); only 5 pts (24%) were ponatinib (pona)-exposed. Switch to asc occurred for sole intolerance in 9 pts (43%) and for resistance in 12 (57%) At baseline, 55% of pts had BCR::ABL1^IS >1%; 20% of pts had major molecular response (MMR) or better. After 25 months of median follow-up and duration of therapy, most pts (81%) remained on asc. Reason for discontinuation was resistance (n=2) and death (n=2; 1 progressed to myeloid blast crisis, MBC). The cumulative incidence (CI) of MR2 at 12, 24 and 48 weeks was 18%, 64% and 82%, respectively; the CI of MMR was 13%, 44% and 50%, respectively. Overall, 80% of pts improved baseline response; loss of best response was observed in 0 and 50% of I and R pts, respectively, and in 23% and 40% of pona-naïve and -exposed pts, respectively. At baseline, mutational status was assessed by Sanger sequencing in 8/12 R pts and 3/8 (38%) harbored ABL mutations (n=2 T315I, n=1 G250E); none of these 3 pts achieved MMR (2 died, 1 was still on asc without alternative therapy). Of 5/8 pts without baseline mutations: 1 achieved stable MMR, 2 stable MR2 and 2 stopped asc due to resistance with new mutations detected (n=1 T315I/R483Q compound mutation, n=1 G254W and RUNX1 mutations - the latter identified only by next-generation sequencing). In our real-world mono-center experience, asc improved molecular response in most cases with excellent tolerance also in very elderly and comorbid pts. The benefit was seen especially in pts without history of resistance or pre-treated with pona and in absence of mutations including T315I. More data are needed to elucidate the role of emerging asc-resistant mutations.