Starting treatment for chronic myeloid leukemia (CML) can be tough. Many people don't get their disease under control well enough, or they have side effects that make life difficult. The goal is to find a treatment that works well and is easy to live with for the long term. In a major trial, a new drug called asciminib was compared to the standard first-line treatments. After about two years, significantly more people taking asciminib achieved a deep level of disease control called a major molecular response, compared to those on the standard drugs. This was true whether asciminib was compared to all standard drugs together, or just to the older drug imatinib. The side effect profile also looked better. Fewer people on asciminib needed to reduce their dose or temporarily stop treatment compared to those on newer, 'second-generation' standard drugs. People were also less likely to have to stop asciminib completely because of side effects compared to those second-generation drugs. With this longer follow-up, asciminib continued to show a better balance of benefits and risks than the current standard treatments for newly diagnosed CML.
Could a new leukemia drug work better and cause fewer side effects than current treatments?
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A new drug for chronic myeloid leukemia showed better disease control and fewer treatment-disrupting side effects than current standard options. What this means for you:
A new drug for chronic myeloid leukemia showed better disease control and fewer treatment-disrupting side effects than current standard options. View Original Abstract ↓
Many patients receiving frontline tyrosine kinase inhibitors (TKIs) for chronic-phase chronic myeloid leukemia (CML-CP) experience inadequate disease control and/or adverse events (AEs) that impair quality of life. Treatments offering optimal efficacy, safety, and tolerability will support long-term therapy. In the primary analysis from the ASC4FIRST trial, a phase 3 randomized trial comparing asciminib with investigator-selected TKIs (IS-TKIs) in newly diagnosed CML-CP, asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. In the secondary analysis (2.2 years' median follow-up), major molecular response (MMR) rate at week 96 was 74.1% with asciminib vs 52.0% with IS-TKIs (treatment difference, 22.4% [95% confidence interval (CI), 13.6-31.3]; 1-sided P< .001) and 76.2% with asciminib vs 47.1% with imatinib in the imatinib stratum (treatment difference, 29.7% [95% CI, 17.6-41.8]; 1-sided P< .001), meeting both key secondary objectives. MMR rate was 72.0% with asciminib vs 56.9% with second-generation (2G) TKIs (treatment difference, 15.1% [95% CI, 2.3-28.0]; 1-sided P< .05), suggesting possible clinical benefit, although the study was not designed to formally confirm statistical significance for this secondary end point. Safety/tolerability remained favorable with asciminib vs IS-TKIs. Dose reductions and interruptions, respectively, occurred with asciminib (18.5%; 46.5%), imatinib (23.2%; 47.5%), and 2G TKIs (54.9%; 63.7%). The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215-0.997). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP. This trial was registered at www.clinicaltrials.gov as NCT04971226.