| Abstract: |
Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients with CML-CP treated with ≥2 prior TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. Consistent with previously published primary analysis results, after a median follow-up of 2.3 years, asciminib continued to demonstrate superior efficacy and better safety and tolerability than bosutinib. The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53–32.95; two-sided p = 0.001). Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs. [Figure not available: see fulltext.]. © 2023, The Author(s). |
| Keywords: |
adult; controlled study; treatment outcome; treatment response; major clinical study; constipation; drug tolerability; fatigue; neutropenia; diarrhea; drug efficacy; drug safety; hypertension; hypophosphatemia; side effect; follow up; follow-up studies; demography; pain; anemia; protein kinase inhibitor; nausea; randomized controlled trial; thrombocytopenia; vomiting; myalgia; creatinine; creatinine blood level; chronic myeloid leukemia; protein tyrosine kinase inhibitor; abdominal pain; arthralgia; asthenia; backache; coughing; dizziness; dyspnea; fever; pruritus; rash; protein kinase inhibitors; alanine aminotransferase; aspartate aminotransferase; insomnia; maculopapular rash; patient care; disease severity; thorax pain; peripheral edema; flu like syndrome; headache; dyspepsia; muscle spasm; dry skin; leukemia, myelogenous, chronic, bcr-abl positive; amylase; upper respiratory tract infection; triacylglycerol lipase; rhinopharyngitis; myeloid leukemia; decreased appetite; leukemia, myeloid, chronic-phase; bosutinib; upper abdominal pain; major molecular response; humans; human; article; oropharynx pain; asciminib; chronic phase chronic myeloid leukemia; tyrosine protein kinase inhibitors; major cytogenetic response; pain in extremity
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