Real-World Use of Frontline BTK Inhibitor Therapies

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Real-world evidence studies provide valuable insights into chronic lymphocytic leukemia treatment patterns and outcomes outside the controlled clinical trial environment, although they require careful interpretation due to methodology limitations and potential publication bias. The Flatiron Database analysis presented at the American Society of Clinical Oncology Annual Meeting demonstrated superior real-world performance of second-generation BTK inhibitors (acalabrutinib and zanubrutinib) compared with first-generation ibrutinib in terms of treatment duration and time to next therapy. Although suggesting potential advantages for zanubrutinib, the small sample sizes limit definitive conclusions about comparative effectiveness between second-generation agents.

Community oncology database studies revealed trends toward lower infection rates with continuous BTK inhibitor monotherapy compared with venetoclax-plus-obinutuzumab combinations, although these findings require contextual interpretation. The neutropenia observed with time-limited therapy often does not translate to febrile neutropenia in clinical practice, and infection risk remains highest during the initial 6 months when disease is most active. These real-world observations help validate clinical trial findings and identify potential late effects not captured in formal studies.

The value of real-world evidence lies primarily in hypothesis generation and validation of clinical trial results rather than immediate practice changes. When real-world findings mirror clinical experience, they provide additional confidence in treatment selection and help understand outcomes in broader patient populations with less intensive monitoring than clinical trial participants. These studies complement randomized controlled trial data by providing insights into treatment patterns, duration, and outcomes in diverse health care settings, supporting evidence-based treatment decisions in routine clinical practice.