Clinical trialPhase 3Leukaemia

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia

N Engl J Med · 2024405 patients (201 asciminib, 204 investigator-selected inhibitor)

Hochhaus A, Wang J, Kim DW, et al. N Engl J Med. 2024. 391:885-898

A newer report of this study has been published: Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial (2026)

Study type: Clinical trial
Study name: ASC4FIRST
Phase: Phase 3
Design: Randomised (1:1), open-label trial, stratified by ELTS score and by the tyrosine kinase inhibitor chosen by the investigator before randomisation
Sample size: 405 patients (201 asciminib, 204 investigator-selected inhibitor)
Source: N Engl J Med · 2024
Trial registration: NCT04971226

In plain words

Asciminib is a new oral medicine for chronic myeloid leukaemia that attaches to a different part of the faulty BCR::ABL1 protein. In this study, newly diagnosed patients who took asciminib were more likely to reach a major molecular response (a large fall in the amount of the disease gene in the blood) after one year, and fewer had to stop the medicine because of side effects. A faster and deeper response may in future raise the chance of "treatment-free remission".

Key results

67.7% vs 49.0%

MMR at week 48 (overall)

Difference 18.9 percentage points (95% CI 9.6 to 28.2); P<0.001

69.3% vs 40.2%

MMR at week 48 (imatinib stratum)

Difference 29.6 percentage points (95% CI 16.9 to 42.2); P<0.001

66.0% vs 57.8%

MMR at week 48 (second-generation stratum)

Difference 8.2 percentage points (95% CI -5.1 to 21.5); not a formal comparison

4.5%

Discontinuation due to adverse events

Versus 11.1% with imatinib and 9.8% with second-generation inhibitors

Drugs in this study:Dasatinib (Sprycel)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 tyrosine kinase inhibitor

One of these drugs, continuously: imatinib 400 mg once daily with food; nilotinib 300 mg twice daily fasting; dasatinib 100 mg once daily; or bosutinib 400 mg once daily with food.

Source of the regimen details: Abstract of the paper (asciminib 80 mg once daily) and ClinicalTrials.gov NCT04971226 (doses of the comparator drugs)

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 chronic myeloid leukaemia (CML) with no prior tyrosine kinase inhibitor therapy.

Endpoints

Primary endpoints: major molecular response (MMR; BCR::ABL1 ≤0.1% on the International Scale) at week 48, comparing asciminib with all investigator-selected inhibitors and with imatinib in the imatinib stratum.

Safety and side effects

Grade 3 or higher adverse events occurred in 38.0% with asciminib versus 44.4% with imatinib and 54.9% with second-generation inhibitors; discontinuation due to adverse events in 4.5%, 11.1% and 9.8%, respectively.

Clinical significance and place in guidelines

On the basis of this study, the FDA granted accelerated approval to asciminib (Scemblix) in October 2024 for adults with newly diagnosed chronic-phase Philadelphia chromosome-positive CML (continued approval contingent on confirmatory data). Asciminib is now one of the first-line options alongside imatinib and second-generation inhibitors; the ELN 2020 recommendations were published before these data and list asciminib only for later lines.

Limitations

Follow-up in this report is short (about 16 months) and the primary endpoint is molecular response, not survival. The study was open-label. Superiority over second-generation TKIs was not formally tested and the difference in this stratum is not statistically conclusive.

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.