https://orcid.org/0000-0001-5369-1501
Key Points
The prevalence of myeloid CHIP in patients with CLL was 12% in untreated and 24% in treated patients (85% with prior chemotherapy exposure)
The presence of two or more M-CHIP mutations was associated with survival, even accounting for prior treatment and age
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.
