Chapters Transcript Video Jennifer Brown, MD, PhD discusses results form the ALPINE trial Symptom-based progression-free survival (S-PFS) as a clinically relevant and patient-centric endpoint in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) Just a reminder, the Alpine trial compared zibrutinib with ibrutinib in patients with relapse CLL who had a median of one prior therapy and showed that zibrutinib had a longer duration of remission and progression free survival than ibrutinib in this setting. The initial analysis of patient reported outcomes, which, you know, are surveys that patients take during treatment to tell us how they're feeling, how their symptoms are. Demonstrated that there were clinically meaningful improvements in their general health status, their physical and role functioning, and their level of fatigue for the patients on zibrutinib compared to ibrutinib. So in this analysis that we're reporting at this Ash we're examining the association between the change in their symptoms over time as reported by the patients and the time to disease progression, and namely progression free survival, and we'll try to identify the most relevant disease symptoms that are measured by these outcomes that actually predict these disease progression. So the analytical model estimates the probability of patients experiencing symptom worsening over time and then combines that with data from the progression-free survival analysis from the trial. And then the goal is to estimate the prognostic association, if any, between the symptoms of deterioration that might be reported by the patients and the time to their disease progression. So this resulted in some quite interesting findings, namely we did find that deterioration over time in fatigue, insomnia, and nausea, vomiting, as well as general physical functioning were all associated with increased risk of disease progression, as we might expect, but it was good to be able to show this from the actual data. Furthermore, zibrutinib was associated with a lower probability of worsening of general health status and quality of life, as well as worsening of nausea and vomiting compared to ibrutinib. And so we were able to see that similar to progression-free survival being better with sanibrutinib, there was an um difference in terms of the symptoms. And again, this analysis did show that progression-free survival was improved with that ibrutinib compared to ibrutinib. So the findings support that there's an association between worsening of patient reported symptoms on official surveys that have been validated and disease progression. So this means that we could potentially use deterioration or worsening of patient reported fatigue, insomnia, or nausea in. Thinking about how likely it is that they may have disease progression upcoming. The patients on zanibrutinib did do better than ibrutinib, so we were also able to model that successfully. And so hopefully in the future, these types of analysis will be able to be used as part of composite endpoints that measure quality of life together with Treatment outcomes for patients with CLL as well as other diseases. Published December 18, 2025 Created by Related Presenters Jennifer Brown, MD, PhD Medical Oncology View Full Profile