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News|Articles|September 11, 2026

Asciminib Maintains Superior MMR and Favorable Safety at 3 Years in Newly Diagnosed Ph+ CML

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Key Takeaways

  • All comparisons favored asciminib for week-144 MMR, including imatinib stratum 79.2% vs 47.1% and second-generation stratum 75.0% vs 59.8%.
  • Deep responses increased over time, with BCR::ABL1IS ≤0.01% in 55.7% vs 36.3% and MR4.5 in 42.3% vs 24.5%.
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The ASC4FIRST trial continued to show higher molecular response rates and better tolerability with asciminib than with standard TKIs in Ph-positive CML.

Asciminib continued to produce superior major molecular response (MMR) rates and a more favorable safety profile compared with investigator-selected TKIs in patients with newly diagnosed Philadelphia chromosome (Ph)–positive chronic-phase chronic myeloid leukemia (CP-CML), according to the week 144 analysis of the phase 3 ASC4FIRST trial (NCT04971226).¹

The data, first presented at the 2026 ASCO Annual Meeting and the 2026 EHA Congress, were also displayed in a poster at the 2026 SOHO Annual Meeting. At a median follow-up of approximately 3.1 years and a data cutoff of September 29, 2025, the MMR rate with asciminib (n = 201) was 77.1% vs 53.4% with all investigator-selected TKIs (n = 204; difference, 23.9%; 95% CI, 15.2%-32.6%; P < .001), continuing the superiority with asciminib over investigator-selected TKIs that was first shown in the trial’s week 48 primary and week 96 key secondary analyses. Rates of deep molecular response, defined as a BCR::ABL1 International Scale of 0.0032% or lower (MR4.5) rates also continued to separate over time, reaching 42.3% with asciminib vs 24.5% with all investigator-selected TKIs.

How was ASC4FIRST designed, and what did the earlier analyses show?

Asciminib is a BCR::ABL1 inhibitor that targets the ABL myristoyl pocket rather than the ATP-binding site targeted by imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Sprycel), bosutinib (Bosulif), and other approved TKIs, a mechanism designed to improve efficacy and reduce off-target effects. ASC4FIRST randomly assigned 405 adult patients with newly diagnosed, treatment-naive Ph-positive CP-CML 1:1 to receive asciminib at 80 mg once daily or an investigator-selected TKI at standard label doses (imatinib at 400 mg daily, nilotinib at 300 mg twice daily, dasatinib at 100 mg daily, or bosutinib at 400 mg daily), stratified by pre-randomization TKI selection (imatinib or a second-generation TKI) and ELTS risk category.

ASC4FIRST Week 144 Analysis: Key Takeaways

  • At a median follow-up of approximately 3.1 years, asciminib maintained superior MMR and deep molecular response rates over investigator-selected TKIs in newly diagnosed Ph-positive CP-CML.
  • The 3-year event-free survival rates favored asciminib, whereas the overall and progression-free survival outcomes were comparable between arms.
  • Safety and tolerability, including rates of hypertension and arterial occlusive events, remained more favorable with asciminib than with imatinib or second-generation TKIs with longer follow-up.

In the previously reported primary and key secondary analyses, asciminib produced a higher week 12 early molecular response rate than all investigator-selected TKIs (89.6% vs 70.1%, respectively) and a higher week 96 MMR rate within both the imatinib stratum (76.2% vs 47.1%, respectively; difference, 29.7%; 95% CI, 17.6%-41.8%; P < .001) and the second-generation TKI stratum (72.0% vs 56.9%, respectively; difference, 15.1%; 95% CI, 2.3%-28.0%; P < .05).2,3 These findings formed part of the basis for the 2024 accelerated FDA approval of asciminib for newly diagnosed CP-CML.4

What molecular response and long-term outcome data emerged at week 144 in ASC4FIRST?

More patients remained on treatment with asciminib (78.6%) than with investigator-selected TKIs overall (55.9%) at the week 144 cutoff.1 Additionally, fewer patients discontinued treatment due to unsatisfactory therapeutic effect with asciminib (10.4%) than with all investigator-selected TKIs (23.0%). MMR rates continued to rise over time and remained higher at week 144 with asciminib across all 3 comparisons. These respective rates were 79.2% vs 47.1% within the imatinib stratum (difference, 32.6%; 95% CI, 20.8%-44.5%; P < .001), and 75.0% vs 59.8% within the second-generation TKI stratum (difference, 15.2%; 95% CI, 2.6%-27.8%). Deep molecular response rates showed a similar pattern, with rates of BCR::ABL1International Scale of 0.01% or lower reaching 55.7% with asciminib vs 36.3% with all investigator-selected TKIs, and the MR4.5 rates reaching 42.3% vs 24.5%, respectively. The 3-year Kaplan-Meier estimates showed event-free survival rates favoring asciminib (85.0% [95% CI, 79.7%-89.5%] vs 69.2% [95% CI, 62.7%-75.4%] with all investigator-selected TKIs), whereas the 3-year overall survival (99.0% [95% CI, 96.0%-99.7%] vs 97.2% [95% CI, 93.5%-98.9%]) and progression-free survival (98.0% [95% CI, 94.7%-99.2%] vs 94.8% [95% CI, 90.4%-97.2%]) rates were comparable between these respective arms.

What did the ASC4FIRST week 144 mutation and safety analyses show?

No new postbaseline treatment-emergent BCR::ABL1 mutations were observed with asciminib after the week 96 cutoff, compared with 1 new mutation each with imatinib ( BCR::ABL1 E459K) and with a second-generation TKI (BCR::ABL1 F359V). Safety and tolerability remained more favorable with asciminib (n = 200) than with imatinib (n = 99) or second-generation TKIs (n = 102) by week 144, with generally lower rates of grade 3 or higher adverse effects (AEs), serious AEs, and AEs leading to dose adjustment, interruption, or discontinuation. AEs of special interest, including myelosuppression, gastrointestinal toxicity, and hepatotoxicity, were also generally less frequent with asciminib than with the control agents.

All-grade hypertension occurred in 12.5% of patients receiving asciminib vs 6.5% of those treated with all investigator-selected TKIs, and grade 3 or higher hypertension occurred in 6.0% vs 3.5% of patients, respectively. Cumulative arterial occlusive events by week 144 occurred in 3.5% of patients receiving asciminib, 1.0% of those receiving imatinib, and 2.9% of those receiving a second-generation TKI. No on-treatment deaths were reported during the trial; across survival follow-up, 8 deaths occurred overall (asciminib arm, n = 3, imatinib arm, n = 4, second-generation TKI arm, n = 1), including 1 additional death in the asciminib arm since the week 96 cutoff, which the investigators deemed unrelated to study treatment.

References

  1. Issa G, Cortes J, Hochhaus A, et al. ASC4FIRST week 144 analysis: continued superior efficacy and favorable safety of asciminib vs investigator-selected tyrosine kinase inhibitors in newly diagnosed chronic myeloid leukemia in chronic phase. Presented at: 2026 SOHO Annual Meeting; September 9-12, 2026; Houston, Texas. Abstract CML-1050.
  2. Hochhaus A, Wang J, Kim DW, et al. Asciminib in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2024;391(suppl 10):885-898. doi:10.1056/NEJMoa2400858
  3. Cortes JE, Hughes TP, Wang J, et al. Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial. Blood. 2026;147(13):1433-1446. doi:10.1182/blood.2025029210
  4. FDA grants accelerated approval to asciminib for newly diagnosed chronic myeloid leukemia. FDA. October 29, 2024. Accessed September 11, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-asciminib-newly-diagnosed-chronic-myeloid-leukemia

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