Myeloid clonal hematopoiesis of indeterminate potential in patients with chronic lymphocytic leukemia.

abstractClonal hematopoiesis of indeterminate potential (CHIP) in patients with chronic lymphocytic leukemia (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 analyzed data from patients participating in a prospective CLL database at the 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 analyzed 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). Overall, 747 (77%) patients had NGS performed before CLL treatment, whereas 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 that described in 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 an impact on M-CHIP emergence even in younger patients. The presence of ≥2 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.