How Does Asciminib Compare With Other TKIs in Long-Term CML-CP Care?

Asciminib (Scemblix) is the “treatment of choice” for many patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) who seek improved quality of life and a chance at eventually discontinuing treatment, according to Jorge E. Cortes, MD.

Cortes spoke with CancerNetwork^® about the 144-week analysis of data from the phase 3 ASC4FIRST trial (NCT04971226), which he presented in a poster session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The updated analysis showed that the major molecular response (MMR) rate continued to improve over time with asciminib compared with other second-generation tyrosine kinase inhibitors (TKIs) like imatinib (Gleevec). Overall, the findings highlighted a favorable risk-benefit profile for asciminib vs current standard-of-care options.

According to Cortes, chief of hematology at University of Alabama at Birmingham (UAB) and deputy director of O’Neal Cancer Center at UAB, the analysis showed that asciminib is meeting the high expectations placed upon it as a novel frontline therapy for patients with CML-CP. Regardless, he noted a need to further improve quality of life and offer more possibilities of treatment discontinuation across this population, emphasizing the goal of longer and better lives for patients.

What was the context for this presentation detailing long-term outcomes from the ASC4FIRST trial assessing asciminib among patients with newly diagnosed CML-CP? How does this updated report build upon prior findings seen with asciminib?

Cortes: This was a study that investigated asciminib, a novel TKI, as initial therapy for patients with CML-CP compared to any of the available TKIs approved for frontline therapy. The primary end point was MMR at 48 weeks, and the study met the primary end point. Although that’s an important hallmark, [considering] patients stay on therapy for a long time and probably experience resistance, sometimes adverse events [AEs], etc., the long-term follow-up becomes very important.

This is the first look at the 3-year follow-up of this study, or 144 weeks. The important thing about showing these data is to show how the efficacy continues evolving, the difference between asciminib and the other drugs, as well as the tolerability to make sure that it remains well tolerated and if any AEs that occur with either of these therapies.

Of note, the MMR rate increased over time with asciminib, whereas it was relatively stable with other TKIs. What do these data suggest about the utility of maintaining patients on targeted therapy for extended durations?

What [the data] show is that, first, we haven’t reached a plateau [or] a maximum response rate with asciminib. It would be expected that it’ll take some time before we reach that. But it is also important to remind us that although we are always aiming for the deepest responses, we get there eventually, so maintaining patients on therapy, especially if they’re tolerating the treatment well, is important as we get to those deep responses. They’re not going to happen in the first year. They may happen in a few patients—sometimes, they do—but the important thing is the perseverance [to] continue therapy. We don’t know how far these responses are going to go. We are close to 80% with the MMR and about 50% in the MR4, which is the deep molecular response. Very encouraging, but they are still going up, so we’ll see how far they can go.

From a practical, multidisciplinary clinic perspective, how does asciminib lower toxicity burden and redefine what clinicians should expect from long-term frontline tolerability, particularly when compared to second-generation TKIs?

That’s been a very good asset of asciminib: the fact that it has a good safety profile and it’s well tolerated. Most patients can continue therapy and experience very little or no [AEs]. The treatment discontinuation due to AEs is half as frequent or even less than with the other TKIs. We are trying to get as many patients off therapy by improving their response, but realistically, many patients will remain on treatment for a long time, so better tolerability becomes very valuable. We’ve had some complementary data showing quality of life, patient-reported outcomes, other elements like the percentage of days that the patient stays without AEs, and so on. All of this showed that [asciminib is] better tolerated. That’s good news for the patients who are going to be taking the drug for a long time.

Do these data cement STAMP inhibition as the definitive frontline standard of care for newly diagnosed CML-CP? How might these results translate into successful treatment-free remission attempts?

[The study] cements the high expectations that we had for asciminib as frontline therapy, and it shows that, indeed, it is meeting those expectations. We are [quite] fortunate to have many good treatment options. There are patients who will continue using imatinib or some of the other second-generation TKIs for a variety of reasons. It is good to know that we have good options, but with these data, asciminib is the treatment of choice for a large percentage of patients who are aiming for better quality of life and…a better probability of treatment discontinuation, which is increasingly a goal of therapy for many of our patients.

What do you ultimately hope colleagues take away from these updated findings, particularly as they relate to the evolving role of targeted therapy in CML management?

The takeaway message is that we shouldn’t be complacent with the fact that we have good outcomes with imatinib. [A]s I said, it’s a very good therapy, but we are not done with our aims to improve the treatment until we work on a much higher rate of treatment discontinuation [and] on improving the quality of life of the patients. These are goals that have become the most important ones; it’s no longer just about survival. Yes, we have a near normal life expectancy for the patients, but patients also want to live better, not just live more. We need to continue looking for better ways to help the patients live a longer—but also a better—life.

Reference

Cortes JE, Hochhaus A, Takahashi N, et al. ASC4FIRST wk 144 analysis: efficacy and safety and tolerability with asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed (ND) chronic myeloid leukemia in chronic phase (CML-CP). J Clin Oncol. 2026;44(suppl 16):6583. doi:10.1200/JCO.2026.44.16_suppl.6583