Background: Real-world data are an essential complement to clinical trials. This is particularly true for chronic lymphocytic leukemia, where five first-line options have never been directly compared.
Methods: The authors present the results of a national multicenter real-world study focusing on treatment choices in frontline chronic lymphocytic leukemia (CLL) and the criteria underlying this choice. Patients' medical records were included over a 6-month period in 25 centers.
Results: The majority of patients received obinutuzumab and venetoclax, especially those with mutated IGHV status. Patients harboring TP53 alterations were almost all treated with Bruton tyrosine kinase inhibitors, with a preference for zanubrutinib. Patients initiated on continuous Bruton tyrosine kinase inhibitors (BTKi) regimens were significantly older; second-generation BTKi, acalabrutinib and zanubrutinib were mostly prescribed. The most cited choice criteria by physicians were genetic prognostic factors, followed by fixed treatment duration and patient logistics considerations. Multiple correspondence analysis and unsupervised hierarchical clustering analysis allowed to identify two distinct patient profiles: younger patients, mostly with mutated IGHV status, who were mainly treated with combined drug regimens due to their fixed duration, and older patients, largely treated with BTKi because of the possibility of outpatient management.
Conclusion: This study is the first to report real-world evidence on treatment choice in first-line CLL and highlight two distinct groups of patients.
Keywords: chronic lymphocytic leukemia; first‐line treatment; physician decisions; real‐world evidence.
© 2026 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.