Treatment with Asciminib As a Second Line after One Prior Tyrosine Kinase Inhibitor (TKI) in Patients with Chronic-Phase Chronic Myeloid Leukemia (CML-CP) - a Chart Review Study in the United States

Introduction: In CML-CP, first-line treatment switching due to intolerance or resistance is frequent with ATP-competitive TKIs and patients typically experience poor response rates in second-line and beyond. Treatments that optimize tolerability and efficacy are needed to allow patients to stay on therapy and achieve treatment goals. Asciminib, an ABL/BCR::ABL1 TKI targeting the ABL myristoyl pocket is approved for patients with CML-CP previously treated with ≥2 TKIs or with the T315I mutation, recently demonstrated positive phase 3 study results in newly diagnosed CML (ASC4FIRST), and is being assessed in clinical trial of patients previously treated with one TKI (ASC2ESCALATE). Here we describe real-world clinical outcomes of patients treated with asciminib after one prior TKI in the US. Methods: In this retrospective panel-based chart review study, eligible oncologists/hematologists from the US with experience treating patients with CML reported de-identified data via an online case report form from February to April 2024. Eligible adult patients with CML-CP did not have the T315I mutation and initiated asciminib (index) between January 2022 and June 2023 after one prior TKI. Time to treatment discontinuation, and time to BCR::ABL1 ≤0.1% (MR3 or better; major molecular response) and BCR::ABL1 ≤1% (MR2 or better) were measured using Kaplan-Meier analyses. BCR::ABL ≤0.01% (MR4 or better, including undetectable; deep molecular response) as best response, progression to accelerated phase/blast crisis (AP/BC), and adverse events (AEs; any grades) were also assessed. Subgroup analyses were conducted in patients who discontinued the first TKI due to resistance/suboptimal response, and by first- or second-generation (1G/2G) TKI as first TKI. Results: A total of 149 eligible patient charts reported by 51 physicians (49.0% community, 51.0% academic; 82.4% ≥10 years of practice) were reviewed. The 149 patients had median age 63.0 years and were 45.0% female, 56.4% White, 24.2% Black/African American, and 15.4% Hispanic/Latino. At CML diagnosis, 65.8% had an intermediate-risk and 12.8% a high-risk Sokal score, and 11.4% had ECOG performance score ≥2. Patients received imatinib (48.3%), dasatinib (38.9%), nilotinib (9.4%), or bosutinib (3.4%) as first TKI, with a median treatment duration of 52.1 weeks. The primary reason for first TKI discontinuation included resistance (43.6%), suboptimal response (34.9%), and intolerance/management of adverse events (4.7%). Asciminib was initiated at 40 mg twice daily by 42.3% and 80 mg once daily by 43.6% of patients. By 48 weeks post index, 93.3% of patients remained on asciminib (resistance/suboptimal response to first TKI: 93.7%; 1G TKI as first TKI: 92.9%; 2G TKI as first TKI: 93.7%). Median time to MR3 or better was 35.0 weeks and the median time to MR2 or better was 21.4 weeks. By 48 weeks post index, 68.2% of patients achieved or maintained MR3 or better (resistance/suboptimal response to first TKI: 70.2%; 1G TKI as first TKI: 61.6%; 2G TKI as first TKI: 73.1%) and 87.8% of patients achieved or maintained MR2 or better (resistance/suboptimal response to first TKI: 92.6%; 1G TKI as first TKI: 86.0%; 2G TKI as first TKI: 88.9%). Over a median follow-up of 50.8 weeks, MR4 or better was achieved by 45.0% of patients as best response on asciminib (resistance/suboptimal response to first TKI: 49.5%; 1G TKI as first TKI: 40.3%; 2G TKI as first TKI: 49.4%), and no patients were observed to progress to AP/BC post index. Constitutional AEs including fatigue (8.7%), headache (4.7%), rash (3.4%) and abdominal pain (2.0%); gastrointestinal AEs including nausea (8.7%), diarrhea (5.4%) and vomiting (5.4%); and cytopenia (4.0%) were observed post index. Conclusions: This real-world study of asciminib demonstrated that over two-thirds of patients achieved or maintained MR3, and nine out of ten patients reached the key response milestone goal of MR2 by 48 weeks, despite inclusion of a majority with resistance/suboptimal response to a prior TKI. Deep molecular response was reported as the best response for nearly half of patients during the first year of treatment with asciminib. Low discontinuation rates, regardless of type of prior TKI used, and low frequency of AEs were observed post asciminib initiation. These results suggest that asciminib is well-tolerated and rapidly effective among patients with CML who received one prior TKI in the US clinical practice.

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