Clinical trialPhase 3Leukaemia

Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial

Blood · 2026

Cortes JE, Hughes TP, Wang J, Kim DW, Kim DDH, Mayer J, et al. Blood. 2026. 147:1433-1446

Study type: Clinical trial
Study name: ASC4FIRST
Phase: Phase 3
Design: Secondary analysis of a randomised trial (median follow-up 2.2 years) versus investigator-selected tyrosine kinase inhibitors
Source: Blood · 2026
Trial registration: NCT04971226

In plain words

Asciminib is a newer oral medicine for CML. After about two years, three quarters of patients taking asciminib had reached a major molecular response, compared with about half of patients taking older medicines, and fewer needed a lower dose or had to stop the medicine because of side effects. Long-term survival data are not yet available.

Key results

74.1% vs 52.0%

MMR at week 96 (versus all TKIs)

Difference 22.4%; one-sided P<0.001

76.2% vs 47.1%

MMR at week 96 (imatinib stratum)

Difference 29.7%

72.0% vs 56.9%

MMR versus second-generation TKIs

The study was not designed to formally test this comparison

Drugs in this study:Imatinib (Gleevec)Nilotinib (Tasigna)

Dose and schedule cards

Asciminib

Philadelphia-positive chronic-phase CML in adults: newly diagnosed (ASC4FIRST), previously treated, or with the T315I mutationCycle length: ContinuousOn the page “Leukaemia” · Treatment regimens and dosing in CML

Philadelphia-positive chronic-phase CML in adults: newly diagnosed (ASC4FIRST), previously treated, or with the T315I mutation

Drug	Dose	Route	Schedule
Newly diagnosed or previously treated
Asciminib	80 mg once daily or 40 mg twice daily	Oral, on an empty stomach	Continuous
T315I mutation
Asciminib	200 mg twice daily	Oral, on an empty stomach	Continuous

Cycle length: Continuous
Duration: As long as there is clinical benefit, or until unacceptable toxicity

No food from 2 hours before until 1 hour after each dose. Dose reduction for adverse reactions: 40 mg once daily or 20 mg twice daily (in T315I: 160 mg twice daily); inability to tolerate these doses: discontinue permanently. The FDA first-line approval is based on major molecular response (accelerated approval).

On the page “Leukaemia” · Treatment regimens and dosing in CML

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Asciminib

Asciminib 80 mg orally once daily fasting, continuously.

2Investigator-selected TKI (imatinib or a second-generation TKI)

One of these drugs, chosen by the investigator before randomisation, continuously: imatinib 400 mg once daily with food; nilotinib 300 mg twice daily fasting; dasatinib 100 mg once daily with or without food; or bosutinib 400 mg once daily with food.

Source of the regimen details: ASC4FIRST trial regimen: ClinicalTrials.gov NCT04971226

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with newly diagnosed chronic-phase Philadelphia chromosome-positive CML with no prior tyrosine kinase inhibitor therapy; 1:1 randomisation stratified by ELTS score and by the TKI selected before randomisation.

Endpoints

Major molecular response (MMR) at week 96 versus all TKIs and versus imatinib (key secondary endpoints); safety and tolerability.

Safety and side effects

Dose reductions and treatment interruptions, respectively: asciminib 18.5% and 46.5%, imatinib 23.2% and 47.5%, second-generation TKIs 54.9% and 63.7%. The hazard ratio for time to discontinuation due to adverse events for asciminib versus second-generation TKIs was 0.46.

Clinical significance and place in guidelines

This report confirms the higher molecular response rates and better tolerability of first-line asciminib with 96 weeks of follow-up; the ELN 2025 recommendations list it among the first-line options alongside imatinib and second-generation TKIs, noting that long-term survival data are not yet available.

Limitations

The 96-week endpoint is a surrogate (molecular response) and overall survival data have not yet been reported.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.