Asciminib in newly diagnosed Philadelphia chromosom–positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP): A retrospective chart review study in the US.

e23076 Background: Asciminib, the first BCR:ABL1 inhibitor specifically targeting the ABL myristoyl pocket, received US FDA approval in October 2024 for the treatment of adults with newly diagnosed Ph+ CML-CP based on the Phase 3 ASC4FIRST trial (NCT04971226). Asciminib was initially approved by the US FDA in October 2021. This is the first study to assess real-world clinical outcomes of patients treated with asciminib as first-line (1L) for CML-CP in US clinical practice. Methods: This retrospective, physician panel-based chart review included adult patients with CML-CP without T315I mutation who initiated asciminib as 1L (index date) between January and October 2024. De-identified data were contributed by experienced US hematologists and oncologists from community and academic centers using an online case report form between June and September 2025. Time to treatment discontinuation and time to molecular response, specifically BCR:ABL1 ≤1% (MR2 or better), ≤0.1% (MR3 or better) and ≤0.01% (MR4 or better), were assessed using Kaplan–Meier methods. Results: Overall, 30 physicians (53.3% academic, 46.7% community) from all US regions (33.3% Midwest, 30.0% South, 20.0% Northeast, 16.7% West) provided 98 charts for patients with CML-CP who initiated asciminib as 1L (Table). Most started with 80 mg daily dose (51.0% 80 mg QD, 33.7% 40 mg BID), and 13.3% initiated low dose asciminib (40 mg QD). Median follow-up period was 51.3 weeks (range: 28.1, 81.1). By 48 weeks post-asciminib initiation, the cumulative probability of achieving MR2 was 91.0% (95% CI: 84.1, 95.7; median 17.0 weeks), MR3 was 70.4% (95% CI: 60.6, 79.7; median 32.1 weeks), and MR4 was 42.6% (95% CI: 32.9, 53.9; median not reached). Cumulative probability of asciminib discontinuation by 48 weeks post-index was 7.3% (95% CI: 3.5, 14.7). Two patients discontinued asciminib due to resistance, and none due to adverse events. Cardiovascular-related adverse events were uncommon (hypertension: 4.1%, heart failure: 3.1%, QTC prolongation: 2.0%, cardiac arrhythmias: 1.0%, myocardial infarction: 1.0%). Progression to accelerated phase or blast crisis, or death was not observed. Conclusions: This first, diverse real-world cohort of newly diagnosed patients with CML-CP treated with asciminib demonstrated efficacy outcomes, including deep molecular responses and discontinuation rates consistent with ASC4FIRST. These findings support asciminib’s favorable risk-benefit profile and its role as a standard of care in 1L for CML management in US clinical practice. Patient characteristics. Median or % Age 56 Female 46.9 White / Black / Hispanic / Other 60.2 / 16.3 / 17.3 / 6.1 Sokal low / intermediate / high / unknown 17.3 / 67.3 / 13.3 / 2.0 ECOG 0 / 1 / ≥2 28.6 / 60.2 / 11.2 Hypertension / COPD / Diabetes 30.6 / 12.2 / 7.1 Framingham risk score low / intermediate / high / unknown 31.6 / 51.4 / 6.1 / 8.2