CML-417: ASCEMBL Phase 3 Health-Related Quality of Life (HRQL) Comparison of Asciminib and Bosutinib for Patients with Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated with 2 or More Tyrosine Kinase Inhibitors (TKI)

Abstract

<h3>Context:</h3> Asciminib is a first-in-class potent and specific BCR-ABL1 inhibitor that specifically targets the ABL1 Myristoyl Pocket (STAMP). ASCEMBL, the first controlled study comparing treatments for resistant/intolerant CML-CP, demonstrated that asciminib has a superior efficacy and an improved safety and tolerability profile compared with bosutinib. <h3>Objective:</h3> To evaluate the HRQL impact of asciminib compared with bosutinib at 24 weeks of treatment. <h3>Design:</h3> A phase 3, multi-center, open-label, randomized clinical trial. <h3>Patients:</h3> A total of 157 patients, randomized to asciminib 40 mg twice daily, and 76 patients randomized to bosutinib 500 mg once daily. <h3>Main Outcome Measures:</h3> HRQL was assessed in the intent to treat population with the MD Anderson Symptom Inventory – chronic myeloid leukemia (MDASI-CML), an exploratory endpoint. Additional HRQL measures were included in ASCEMBL and are reported elsewhere. Analyses included mixed model repeated measures (MMRM). <h3>Results:</h3> MMRM analyses on MDASI-CML demonstrated that asciminib patients maintained or improved from baseline on all items (demonstrating improvement on 20 out of 26 items), symptom total score, and symptom distress score. Notable item improvements from baseline included fatigue, mood, and feeling of being upset. HRQL was similar to baseline in the bosutinib arm on symptom total score, symptom distress score, and all items, except for nausea and diarrhea, with treatment differences favoring asciminib. Questionnaire compliance rates at week 24 were high and similar between treatment arms (83.1% <i>vs</i> 82.0%, respectively, for asciminib and bosutinib). <h3>Conclusions:</h3> Asciminib patients showed improvement in treatment-related symptoms and HRQL compared with baseline and relative to bosutinib, within the first 24 weeks of treatment, confirming earlier findings.