In a study reported in The New England Journal of Medicine, Pich et al found that tumor-infiltrating clonal hematopoiesis (TI-CH) was associated with an increased risk of death or recurrence among patients with early-stage non–small cell lung cancer (NSCLC) and poorer overall survival among patients with a range of solid tumors.
As stated by the investigators: “Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients with cancer. CHIP mutations with high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis [TI-CH]. The frequency of TI-CH and its effect on tumor evolution are unclear.”
Study Details and Key Findings
CHIP and TI-CH were characterized in 421 patients with previously untreated early-stage NSCLC from the TRACERx study and in 49,351 patients with solid tumors from the MSK-IMPACT pan-cancer cohort.
Among 421 patients with NSCLC, CHIP mutations were observed in 143 (34%); of these patients, TI-CH was observed in 60 (42%). On multivariate analysis, TI-CH was significantly associated with an increased risk of death or recurrence (adjusted hazard ratio [HR] = 1.80 [95% confidence interval (CI) = 1.23–2.63]) vs absence of CHIP and an increased risk of death or recurrence (adjusted HR = 1.62, 95% CI = 1.02–2.56) vs CHIP in the absence of TI-CH.
Among patients in the MSK-IMPACT pan-cancer solid tumor cohort, 26% of patients with CHIP had TI-CH. And TI-CH was associated with an increased risk of death from any cause (HR = 1.17, 95% CI = 1.06–1.29) vs CHIP in the absence of TI-CH.
TET2 mutation in CHIP was the strongest genetic predictor of TI-CH. These mutations enhanced monocyte migration to lung tumor cells, promoted a myeloid-rich tumor microenvironment in mice, and promoted tumor organoid growth.
The investigators concluded: “TI-CH increased the risk of disease recurrence or death among patients with NSCLC and the risk of death from any cause among patients with solid tumors. TI-CH remodeled the tumor immune microenvironment and accelerated tumor organoid growth, findings that support a role for an aging-related hematologic clonal proliferation in cancer evolution.”
Charles Swanton, MD, PhD, of the Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK, and Elsa Bernard, PhD, of the Computational Clinical Oncology Laboratory, Gustave Roussy, Villejuif, France, are the corresponding authors of The New England Journal of Medicine article.
Disclosure: The study was funded by the Royal Society and others. For full disclosures of the study authors, visit nejm.org.
