Asciminib Shows Improved Patient Outcomes vs Investigator-Selected Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia: ASC4FIRST Trial
Key Clinical Summary
- Population and Design: Phase 3 ASC4FIRST trial evaluated asciminib, a first-in-class STAMP (Specifically Targeting the Myristoyl Pocket) inhibitor, versus approved frontline TKIs (imatinib, nilotinib, dasatinib, bosutinib) in 405 patients with newly diagnosed CML. Patient-reported outcomes were assessed using EORTC QLQ-C30, EQ-5D-5L, and FACT-GP5 tools at baseline, week 4, and week 96.
- Findings: Patients receiving asciminib reported greater improvements in global health status, physical, emotional, and role functioning, and reductions in pain and GI symptoms compared with control TKIs. ~50% of asciminib-treated patients improved in global health, while only 10 to 15% worsened versus ~33% worsening in the control arm.
- Clinical Relevance: Asciminib demonstrated superior patient-reported quality-of-life outcomes alongside its known higher response rates and lower toxicity, reinforcing its role as a well-tolerated, patient-centered frontline therapy for CML patients requiring long-term treatment.
Jorge Cortes, MD, Georgia Cancer Center, Augusta, Georgia, shares patient-reported outcomes from the ASC4FIRST trial, which compared asciminib with standard frontline tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia (CML), at the 2025 ASH Annual Meeting & Exposition in Orlando, Florida.
The analysis demonstrated that patients treated with asciminib reported greater improvements in global health status, functional well-being, and symptom scores over time.
Dr Cortes concluded, “what this study then shows is that overall asciminib provides not only the efficacy that we have seen in the main reports of the ASC4FIRST study with a higher rate of responses, faster responses, deeper responses, fewer side effects, but very importantly that these translate into a better quality of life for the patients.”
Transcript:
Hello, my name is Jorge Cortes from the Georgia Cancer Center at Augusta University in Augusta, Georgia. I'm happy to discuss with you the abstract that we are presenting at ASH that relates to the patient reported outcomes for patients included in the ASC4FIRST study.
This is a very important study because as we all know, one of the main issues that patients face when they're dealing with CML is the impact that the drugs have in the quality of life. Certainly, we want to try to get as many patients off therapy at some point, and we are trying to get the best options for treatment for that. But many patients have to leave with their medication for an extended period of time and for those patients then it is important that the treatment is as well tolerated as possible. That was why we designed this study and what we're presenting in this particular poster.
This comes from the ASC4FIRST study, which investigated asciminib, the first in kind tyrosine kinase inhibitor that specifically targets the myristoyl pocket. That has been approved for patients who have received their prior therapy, but also for the frontline setting. The approval in the frontline setting came from this study called the ASC4FIRST, which was a randomized study of asciminib versus all of the available tyrosine kinase inhibitors approved for frontline therapy, imatinib, nilotinib, dasatinib, poziotinib. This report is from the patient reported outcomes that were obtained throughout the study for patients enrolled in the ASC4FIRST study. There were 405 patients that were included and they got an assessment with a variety of tools for patient reported outcomes. The EORTC, the EQ-5D-5L, FACT-GP5, and others.
The completion rate was very good. They got an assessment at baseline and then at weeks 4 and 96. What we measured was the improvement in their scores at the different time points. What we saw is that generally speaking, the patients that received asciminib got an improvement in most of the areas that were measured by this course, the global health status, the functional, physical, functional, role functional, emotional functional, as well as in the symptom scores, pain, appetite, constipation, diarrhea, et cetera. For the most part, there was an improvement that was more noticeable with asciminib.
Probably the most impactful of all of these is when you look at the global score because it really includes all of these measures into the overall sense of wellbeing by the patients. That clearly showed a benefit for asciminib. About half of the patients improved their global health status and just about 10 or 15% worsen with asciminib, whereas about a third of patients worsened with the control tyrosine kinase inhibitors.
What this study then shows is that overall asciminib provides not only the efficacy that we have seen in the main reports of the ASC4FIRST study with a higher rate of responses, faster responses, deeper responses, fewer side effects, but very importantly that these translates into a better quality of life for the patients. I think this is very important because although we have always focused very importantly on the depth of the response, and that's still very important, we should not forget about the quality of life of the patients, which is something that we recognize more and more that is so important for the patients. When it's not addressed, it can be very limiting for these patients living on therapy for extended periods of time. These are the results that we are presenting, and I hope you find them interesting.
Source:
Cortes J, Hochhaus A, Flynn K, et al. Asciminib (ASC) demonstrates continued improvement in patient-reported outcomes (PROs) vs investigator-selected tyrosine kinase inhibitors (IS-TKIs) in newly diagnosed chronic myeloid leukemia (CML): ASC4FIRST week 96 analysis. Dec 6-9, 2025; Orlando, FL. Abstract: 1997
