Optimizing Frontline Selection and Treatment-Free Remission in CML

Once considered a terminal diagnosis, chronic myeloid leukemia (CML) in chronic phase has been fundamentally rewritten as a highly manageable chronic condition. In this episode of Oncology on the Go, Joshua Zeidner, MD, and Jorge E. Cortes, MD, sat down to explore the rapidly shifting therapeutic paradigm of frontline CML management.

The discussion tracked the monumental evolution of treatment from early bone marrow transplants to the introduction of imatinib (Gleevec) and subsequent generations of tyrosine kinase inhibitors (TKIs). The experts dove deep into the practice-changing data from the phase 3 ASC4FIRST trial (NCT04971226), analyzing how the newly introduced STAMP inhibitor, asciminib (Scemblix), is challenging traditional treatment sequencing due to its superior efficacy and highly favorable toxicity profile.

In the ASC4FIRST trial, the major molecular response (MMR) rate was 74.1% with asciminib vs 52.0% with other investigator-selected TKIs. The MMR rate at week 96 was consistently higher with asciminib vs other investigator-selected TKIs and imatinib across all assessed demographic and prognostic subgroups. Overall, investigators concluded that asciminib demonstrated a favorable risk-benefit profile compared with other standard therapies and presented a “valuable frontline option” for patients with CML in chronic phase.

Zeidner and Cortes also shared practical clinical insights on:

• Shared Decision-Making: Tailoring frontline selections based on patient lifestyle, comorbidities, and preferences.
• Navigating Milestones: Balancing strict NCCN/European LeukemiaNet molecular response guidelines with individualized, real-world context.
• The Art of Discontinuation: Using strategic timing and criteria (such as achieving sustained MR4.5) to optimize success rates for treatment-free remission.
• The Next Frontier: Managing resistance mutations and mapping out second- and third-line therapies in an evolving post-asciminib landscape.

Zeider is professor of medicine, chief of Leukemia Research, and director of Clinical Cancer Research Commercial Integration at the University of North Caroline-Chapel Hill Cancer Therapeutics Research Program. Cortes is associate director for Translation at the University of Alabama O’Neal Cancer Center.

To watch the full discussion, visit: https://www.cancernetwork.com/between-the-lines/oncology-on-the-go-frontline-chronic-myeloid-leukemia-in-chronic-phase-optimizing-treatment

Reference

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(3):1433-1446. doi:10.1182/blood.2025029210