Researchers have found that an incidental finding of clonal hematopoiesis in liquid biopsies can be used to trigger hematologic tests to assess the risk of developing myeloid malignancies, according to a new study published by Tagliamento et al in the European Journal of Cancer. The findings were also presented at the 34th European Organisation for Research and Treatment of Cancer (EORTC)–National Cancer Institute (NCI)–American Association for Cancer Research (AACR) Symposium on Molecular Targets and Cancer Therapeutics (Abstract 22).
Study Background
When tumors shed DNA into the blood—contributing to cell-free DNA—this can be identified in liquid biopsies, enabling physicians to better characterize a cancer, select the optimal therapy, or monitor the progression of disease and its response to treatment without more invasive biopsies taken from the tumor itself.
Clonal hematopoiesis is a relatively common and incidental finding in liquid biopsies, and researchers wondered if these biopsies could also be used systematically to identify patients who either have or could be at higher risk of developing hematologic malignancies such as myelodysplastic syndrome or acute myeloid leukemia. Previous studies have shown that the absolute risk of clonal hematopoiesis progressing to blood cancer is around 1% each year, with a 10-fold increase in relative risk.
Methods and Results
Between March 2021 and October 2021, researchers took liquid biopsies from 1,416 patients with a range of solid tumors who had enrolled in the Gustave Roussy Cancer Profiling study (STING).
“We found that 113 patients (8%) had at least one clonal hematopoiesis mutation that … placed them at higher risk of developing blood cancers during their life. Out of these patients, 45 were referred to our hematology unit by their oncologist, and 5 were subsequently diagnosed with blood cancer: 1 with myelomonocytic leukemia, 2 with myelodysplastic syndrome, and 2 with essential thrombocythemia,” said first study author Marco Tagliamento, MD, a medical oncologist and research fellow at the Institut Gustave Roussy.
The researchers believe that when liquid biopsies reveal a high-risk clonal hematopoiesis feature in patients, this should trigger further hematologic evaluation in some circumstances to reveal the actual risk of developing a blood cancer or to uncover cases where a patient already has one.
Study Implications
“Early detection could prevent complications during anticancer treatments—for instance, alterations to blood counts, and consequent interruptions or delays [in] treatment. It could also indicate possible diagnostic and therapeutic pathways for doctors to consider for hematologic disease,” Dr. Tagliamento suggested.
During the work to identify patients who should be referred for further investigation, each case was considered carefully to identify the genetic mutations involved in clonal hematopoiesis.
“Case-by-case evaluation is crucial. Different aspects must be considered when evaluating the potential impact and management of high-risk clonal hematopoiesis in patients who already have cancer. These relate, for example, to the patients, their medical history, and to the underlying cancers. All of them should be part of a balanced evaluation made for each individual case,” said Dr. Tagliamento. “We will continue to apply this approach within the Gustave Roussy Molecular Tumour Board. We want to implement and improve the efficiency of the algorithm to select patients with solid cancers who could benefit from a hematologic evaluation,” he added.
“This is well-conducted research that reveals an additional facet to the information gained from liquid biopsies. Dr. Tagliamento is right to stress the importance of evaluating the context for each individual patient. Patients [with cancer] have much to worry about, and so their doctors need to take into account the patients’ clinical situations and their treatment plans. Patients’ anxieties mean that it will not always be appropriate to highlight a potential increased risk of developing an additional blood cancer in later years,” said Ruth Plummer, MD, PhD, Professor of Experimental Cancer Medicine at Newcastle University and Chair of the 34th EORTC–NCI–AACR Symposium on Molecular Targets and Cancer Therapeutics, who was not involved in the study. “Only some specific clonal hematopoiesis mutations are likely to predict a higher risk of blood cancer developing at some point in the future. This study suggests [that] patients with these mutations should be referred for further evaluation, and even then, decisions about what would be best for these patients will depend on a range of other factors.”
Disclosure: For full disclosures of the study authors, visit ejcancer.com.
