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Article Abstract
NOTCH1 and SF3B1 mutations are common in CLL, but their prognostic value for overall survival (OS) and progression-free survival (PFS), as well as time to first treatment (TTFT) and treatment-free survival (TFS), remains uncertain. This meta-analysis systematically evaluates their impact. A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed up to March 2025. Relevant study data and prognostic outcomes were extracted, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models based on heterogeneity. A total of 38 studies with 24,060 CLL patients met the criteria. Among them, 32 and 23 studies evaluated the prognostic impact of NOTCH1 and SF3B1 mutations, respectively. Compared to wild-type, NOTCH1 mutations were associated with worse OS (HR = 1.88), PFS (HR = 1.42), TTFT (HR = 1.63), and TFS (HR = 2.46). SF3B1 mutations similarly predicted poor OS (HR = 1.68), with HRs of 1.63, 1.24, and 1.70 for PFS, TTFT, and TFS. Subgroup analysis showed worse OS in older and treatment-naïve patients. These findings suggest that NOTCH1 and SF3B1 mutations are significant adverse prognostic markers in CLL. Increasing evidence supports their inclusion in clinical risk stratification and personalized treatment planning, especially when combined with patient-specific clinical and molecular features.
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