Real-World Selection of Venetoclax-Obinutuzumab Versus BTK Inhibitor Therapy for Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Novel targeted agents have transformed the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including continuous BTK inhibitor (BTKi) therapy and time-limited regimens such as venetoclax-obinutuzumab (Ven-O) and ibrutinib-venetoclax (I + V). However, factors guiding first-line treatment decisions in routine practice remain poorly defined. To describe real-world first-line treatment patterns and identify factors associated with therapy selection. This retrospective, population-based study included consecutive patients initiating first-line therapy for CLL/SLL in 2024 in Alberta, Canada. Among 148 patients with median age 71 years, time-limited targeted therapy was selected for 75 (51%), including Ven-O (n = 73) and I + V (n = 2). Continuous BTKi therapy was used in 65 (44%), while chemotherapy-based regimens were uncommon (n = 8, 5%). Among 138 patients treated with either continuous BTKi or Ven-O, BTKi use was significantly more frequent among those with del(17p)/TP53 mutation (84% vs. 16%, p = 0.0002), age > 75 years (66% vs. 34%, p = 0.0051), and residence > 100 km from an obinutuzumab-initiating cancer center (70% vs. 30%, p = 0.031). Time-limited and continuous targeted therapies are used with similar frequency for CLL/SLL, with selection shaped by age, TP53 aberrations, geography, and patient preferences. These findings highlight the importance of personalized care and the need to reduce access barriers to time-limited strategies.