Overview
Covalent Bruton tyrosine kinase inhibitors (cBTKis) are standard therapies for CLL/SLL, but side effects lead some patients to switch agents. This study evaluated documented rationales for second-line cBTKi switching among 396 patients (9.1% of first-line cBTKi initiators) in the US Flatiron Health Research Database using an LLM to extract free-text clinician notes.
Most switches occurred from first-line ibrutinib; following the switch, 53.5% of patients received acalabrutinib and 41.9% received zanubrutinib. Documented rationales were available for 86.9% of switching patients. Tolerability and adverse events were the most frequent drivers (87.8%), primarily cardiac comorbidities and bleeding were the most frequently documented adverse events. Patient preference was the second most common rationale overall (19.2%), while factors such as disease progression (4.4%) were documented less frequently.
Why this matters
This qualitative study demonstrates that real-world cBTKi class switching in CLL/SLL is primarily driven by adverse events and patient preference rather than disease progression, reflecting personalized management and shared decision-making in routine practice. Additionally, reasons for switching were well documented in academic and community practices.