Safety and efficacy of asciminib in veterans with chronic myeloid leukemia.

Abstract

6591 Background: Asciminib was approved for use in previously treated patients with chronic myeloid leukemia (CML) in 2021. It employs a novel allosteric mechanism that can overcome resistance and intolerance to conventional tyrosine kinase inhibitors (TKIs). We assessed the efficacy and clinical outcomes of asciminib in Veterans with CML following failure of first- and second-generation TKIs. Methods: Utilizing the VA Informatics and Computing Infrastructure (VINCI), we reviewed all 116 Veterans nationwide with a diagnosis of CML who were treated with asciminib prior to August 2025. Demographic and clinical data collected included age at diagnosis, gender, race, prior CML treatments, and BCR-ABL transcript levels at treatment initiation and at 3 and 6 months. Safety outcomes included the development of thrombocytopenia and neutropenia. Mortality data were collected when applicable. Since more than half of the patients were still alive at the time of chart abstraction, median survival could not be reliably estimated (median 3.4 years, lower limit 2.8 years, upper limit NA). We therefore report the restricted mean survival time (RMST). Results: 110 Veterans were included in the analysis after excluding 6 for missing data. The median age at diagnosis was 65 years (IQR, 52–71) and 95% of participants were male (Table 1). 70% of participants received a first-generation TKI as first-line therapy; in the second-line setting, 12% received a first-generation TKI and 83% received a second-generation TKI. The median BCR-ABL level at asciminib initiation was 1.03 (IQR, 0.08–29.95) and decreased to 0.05 (IQR, 0–0.69) at 6 months. 11 patients developed thrombocytopenia and 3 developed neutropenia. Assuming 5 years of follow-up from the start of asciminib, RMST is 3.3 years (standard error, 0.23 years). Conclusions: Asciminib demonstrated clinically meaningful activity in a heavily pretreated Veteran population with CML. By 6 months, the median BCR-ABL level was 0.05%, consistent with major molecular response (MMR; BCR-ABL ≤0.1%), a well-established positive prognostic indicator. Despite prior exposure to multiple therapies, overall survival (using RMST) remained favorable at a mean of 3.3 years following treatment initiation. Rates of any-grade neutropenia and thrombocytopenia were low, supporting a favorable safety profile. Patient characteristics and outcomes. Characteristic Total (N = 110) Age at diagnosis, median (IQR) 65 (52–71) Gender, n (%) Male 105 (95%) Female 5 (4.5%) Race Black 19 (17%) White 85 (77%) American Indian or Alaska Native 1 (0.9%) Unspecified 5 (4.5%) Treatment Exposure First-line therapy 1 st generation TKI 77 (70%) 2 nd generation TKI 33 (30%) Second-line therapy 1 st generation TKI 13 (11.8%) 2 nd generation TKI 91 (82.7%) 3 rd generation TKI (ponatinib) 6 (5.5%) Outcomes Thrombocytopenia 11 (10%) Neutropenia 3 (2.7%) RMST (5 years), years 3.3 (95% CI, 2.9–3.8)