Clonal hematopoeisis of indeterminate potential (CHIP) in patients with CLL has not been extensively characterized. The objective of this study was to describe the prevalence of myeloid CHIP (M-CHIP) in patients with CLL, and to determine its association with time to first treatment (TTFT) and overall survival (OS). We retrospectively analysed data from patients participating in a prospective CLL database at Dana Farber Cancer Institute who had standard of care targeted 95-gene next-generation sequencing (NGS) performed. A schema was devised to classify mutations as M-CHIP related. M-CHIP was analysed as a binary (present/absent) and categorical (>2 vs. 1 vs. 0 mutations) predictor. We included 966 patients (median age at time of NGS 65 years; 38% female). Seven hundred forty-seven (77%) patients had NGS performed prior to CLL treatment, while 219 (23%) had it performed after receiving treatment. Median follow-up time from NGS was 1.9 years. The prevalence of M-CHIP in untreated (12%) and treated (24%) patients with CLL was similar to previous literature. M-CHIP prevalence appeared to increase with age in untreated patients, but appeared consistent across age in treated patients, suggesting that treatment (85% had prior chemotherapy) may have impact on M-CHIP emergence even in younger patients. The presence of two or more M-CHIP mutations was associated with OS, even accounting for prior treatment and age, but was driven by a small subset of patients (N=28). M-CHIP was not associated with TTFT. These findings support continued work into characterizing the effects of M-CHIP in patients with CLL.
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