Vitamin D Supplementation and Treatment-Free Survival in Early-Stage CLL: A Real-World Validation Study.

Background: Patients with early-stage chronic lymphocytic leukemia (CLL) are typically managed with a watch-and-wait strategy, and no intervention has been shown to modify the natural history of the disease. Methods: We analyzed a large real-world cohort derived from Clalit Health Services, including patients diagnosed with early-stage CLL between 2000 and 2022 who were initially managed with active surveillance. Exposure was defined as vitamin D supplementation for at least 6 months during the watch-and-wait period. The primary endpoint was treatment-free survival (TFS). Multivariable time-dependent Cox models and inverse probability of treatment weighting were applied to adjust for baseline differences. Results: The cohort included 5496 patients, of whom 1862 (34%) received vitamin D supplementation. Median age at diagnosis was 72.2 years, and 56% were male. Median follow-up was 46 months. Patients receiving vitamin D demonstrated significantly longer TFS compared with nonusers (median 147 vs. 82 months, Conclusions: In this large real-world validation cohort, vitamin D supplementation was associated with prolonged TFS in patients with early-stage CLL managed with active surveillance. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.