ASC4FIRST
Trial question
What is the role of asciminib in patients with newly diagnosed chronic myeloid leukemia?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 405
405 patients (149 female, 256 male).
Inclusion criteria: patients with newly diagnosed chronic myeloid leukemia.
Key exclusion criteria: cytopathologically confirmed CNS infiltration; impaired cardiac function or cardiac repolarization; history of significant congenital or acquired bleeding disorder unrelated to cancer; major surgery within the last 4 weeks; history of other active malignancy in the last 3 years; chronic pancreatitis; acute liver disease.
Interventions
N=201 asciminib (at a dose of 80 mg once daily).
N=204 investigator-selected TKI (imatinib 400 mg once daily, nilotinib 300 mg BID, dasatinib 100 mg once daily, or bosutinib 400 mg once daily).
Primary outcome
Major molecular response at week 48 in full analysis set
67.7%
49%
67.7 %
50.8 %
33.9 %
16.9 %
0.0 %
Asciminib
Investigator-selected
TKI
Significant
increase ▲
NNT = 5
Significant increase in major molecular response at week 48 in the full analysis set (67.7% vs. 49%; AD 18.9%, 95% CI 9.6 to 28.2).
Secondary outcomes
Significant increase in major molecular response at week 48 within the imatinib stratum (69.3% vs. 40.2%; AD 29.6%, 95% CI 16.9 to 42.2).
No significant difference in major molecular response at week 48 withing the second-generation TKI stratum (66% vs. 57.8%; AD 8.2%, 95% CI -5.1 to 21.5).
Safety outcomes
No significant difference in at least one adverse event.
Conclusion
In patients with newly diagnosed chronic myeloid leukemia, asciminib was superior to investigator-selected TKI with respect to major molecular response at week 48 in the full analysis set.
Reference
Andreas Hochhaus, Jianxiang Wang, Dong-Wook Kim et al. Asciminib in Newly Diagnosed Chronic Myeloid Leukemia. N Engl J Med. 2024 Sep 12;391(10):885-898.
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