Overview
Patients with chronic lymphocytic leukemia (CLL) who have received both BTK inhibitors and BCL2 inhibitors, two important classes of targeted treatments, have limited evidence to guide their next therapy.
Using the US Flatiron Health Research Database and large language models (LLMs), researchers analyzed clinical notes to understand why physicians selected subsequent treatments, including the reasons prior treatments were stopped and the patient- and disease-related factors influencing treatment choices.
In the submitted ASH abstract, disease progression (58%) and treatment intolerance (33%) were the most common reasons for treatment transitions. Subsequent treatment strategies included alternative covalent BTK inhibitors (29%), venetoclax-based therapy (20%), and non-covalent BTK inhibitors (13%). Clinicians also documented limited treatment options (46%) and uncertainty about treatment sequencing (27%).
Patients transitioning because of treatment intolerance had a longer observed time before their next treatment than those transitioning because of disease progression (median 21 versus 15 months). These findings are descriptive and do not establish that the reason for switching treatment caused differences in outcomes.
Why this matters
Traditional real-world studies show which treatments patients receive and in what sequence, but often cannot explain why physicians make those choices. By extracting clinician-documented reasoning from clinical notes, this study provides additional insight into treatment decisions after exposure to both major targeted therapy classes. The findings highlight the complexity of CLL treatment sequencing and the need for additional evidence to guide clinical decisions.