Real-world analysis of asciminib as first-line therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A chart review Study in the United States

Abstract Introduction: Adenosine triphosphate (ATP)-competitivetyrosine kinase inhibitors (TKIs) are treatment options in newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP); however, switching due to intolerance or resistance is frequent. Asciminib, the first BCR::ABL1 inhibitor that works by specifically targeting the ABL myristoyl pocket, received United States (US) Food and Drug Administration approval in October 2024 as first-line (1L) therapy for newly diagnosed CML-CP following positive Phase 3 study results in ASC4FIRST (NCT04971226), in addition to those previously treated for CML-CP or with the T315I mutation. Asciminib is also being studied among patients with newly-diagnosed CML-CP in ASC4START (NCT05456191). Here we present results from the first study assessing treatment patterns and real-world clinical outcomes in newly diagnosed patients receiving 1L asciminib for CML-CP in the US clinical practice. Methods: This retrospective physician panel-based chart review study gathered patient chart data in June and July 2025 on adults with CML-CP who were initiated on asciminib (index) as 1L therapy between January and October 2024. De-identified data were collected from experienced oncologists/hematologists in community and academic practices across the US through an online case report form. Time-to-response by 24 weeks post-index, including BCR::ABL1 ≤1% (MR2 or better), BCR::ABL1 ≤0.1% (MR3 or better) and BCR::ABL1 ≤0.01% (MR4 or better), was assessed separately using Kaplan-Meier analyses. Discontinuation due to resistance or intolerance was also reported. Data collection is ongoing and interim findings are presented. Results: An interim sample of 52 patient charts reported by 21 physicians were collected. Responding physicians practiced in both academic-based (57.1%) and community-based settings (42.9%), with representation from every US census region (Midwest 38.1%, South 23.8%, Northeast 19.0%, and West 19.0%). Most physicians (85.7%) had ≥10 years of experience treating CML. Patients were racially/ethnically diverse (White 65.4%, Black 17.3%, Hispanic 9.6%, Asian 7.7%), and 42.3% were female. Most patients (63.5%) were commercially insured and 32.7% were publicly insured (Medicare 23.1%, Medicaid 17.3%). At CML diagnosis, patients had a median age of 56 years (25.0% ≥65 years), 67.3% had an intermediate-risk and 13.5% a high-risk Sokal score, and 17.3% had Eastern Cooperative Oncology Group (ECOG) performance status ≥2. At initiation of asciminib, 71.2% of patients received 80 mg/day, with 34.6% receiving 40 mg twice daily and 36.5% receiving 80 mg once daily. One-quarter (25.0%) of patients received 40 mg/day at asciminib initiation. Two-thirds (67.3%) had ≥1 comorbidity at asciminib initiation, most commonly hypertension (42.3%) and chronic obstructive pulmonary disease (17.3%), and 55.8% had an intermediate or high Framingham Risk Score. The median follow-up period post-asciminib initiation was 40.8 weeks (range: 28.2–77.7). By 24 weeks post-index, the cumulative probability of achieving MR2 was 70.7% (95% CI: 57.2%–83.1%), MR3 was 44.1% (95% CI: 31.1%–59.7%), and MR4 was 22.1% (95% CI: 12.5%–37.2%). Two patients discontinued treatment due to resistance, and none due to intolerance. No cases of progression to accelerated phase or blast crisis, or death were observed. Chart review is ongoing, and an increased sample size with extended follow-up time will be reported in future analyses. Conclusions: This study of patients receiving 1L asciminib for CML-CP was initiated within the first year following the update of positive pivotal Phase 3 ASC4FIRST data and subsequent FDA approval. This real-world study included a racially and ethnically diverse sample, with a substantial proportion presenting with severe disease. As reported in the Phase 3 trials, early and robust efficacy signals, including time to MR2, MR3, and MR4, were observed following initiation of 1L asciminib. These early real-world findings support the effectiveness and tolerability of asciminib as initial treatment for patients with newly diagnosed CML-CP in the US clinical practice setting. Additional chart review is currently underway, with analyses planned on a larger sample size and extended follow-up to evaluate molecular response.

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