Researchers have found that liquid biopsies, which are increasingly used in the routine care of patients to identify and monitor the progress of cancer, can also detect a disorder of blood cells that places patients at higher risk of developing blood cancers as well.

The findings were presented at the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.

Tumours shed DNA into the blood, and this contributes to what is known as cell-free DNA (cfDNA). cfDNA can be identified in blood samples or ‘liquid biopsies’ taken from patients, enabling doctors to either better characterise a cancer, select the best therapy or monitor the progression of the disease and its response to treatment without more invasive biopsies taken from the tumour itself.

A condition called clonal haematopoiesis (CH) is a relatively common and incidental finding in liquid biopsies, and researchers at the Institut Gustave Roussy (Villejuif, France) wondered if these biopsies could also be used systematically to identify patients who either have or could be at higher risk of developing blood cancers such as myelodysplastic syndrome (a disorder of blood cells originating in the bone marrow) or acute myeloid leukaemia.

CH happens when a cell called a haematopoietic stem cell, which can develop into different types of blood cells and is made in the bone marrow, starts making cells with the same genetic mutation that is different to the genetic pattern of normal blood cells. These cells can also shed DNA into the blood. Previous studies have shown that the absolute risk of CH progressing to blood cancer is around 1% a year, with a 10-fold increase in relative risk.

Between March and October 2021, researchers took liquid biopsies from 1416 patients with a range of solid tumours who had enrolled in the Gustave Roussy Cancer Profiling study (STING). 

Dr Marco Tagliamento, medical oncologist and research fellow at the Institut Gustave Roussy, France, told the Symposium: “We found that 113 patients, 8%, had at least one clonal haematopoiesis mutation that could be considered to place them at higher risk of developing blood cancers during their life. Out of these patients, 45 were referred to our haematology unit by their oncologist and five were subsequently diagnosed with blood cancer: one with myelomonocytic leukaemia, two with myelodysplastic syndrome and two with essential thrombocythaemia.”

The researchers believe that when liquid biopsies reveal a high-risk CH feature in patients, this should trigger further haematological evaluation in some circumstances to reveal the actual risk of developing a blood cancer or to uncover cases where a patient already has one.

“Early detection could prevent complications during anti-cancer treatments, for instance alterations to blood counts, and consequent interruption or delay to treatment. It could also indicate possible diagnostic and therapeutic pathways for doctors to consider for haematological disease,” he said.

During the work to identify patients who should be referred for further investigation, each case was considered carefully by the Gustave Roussy Molecular Tumour Board to identify the genetic mutations involved in CH.

“Case-by-case evaluation is crucial,” said Dr Tagliamento. “Different aspects must be considered when evaluating the potential impact and management of high-risk clonal haematopoiesis 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. 

“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 haematological evaluation. These results are part of a team project led by Dr Mihaela Aldea and Dr Jean Baptiste Micol.”

Professor Ruth Plummer, from Newcastle University, UK, is chair of the 34th EORTC-NCI-AACR Symposium and was not involved with the research. She said: “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. Cancer patients have much to worry about, and so their doctors need to take into account the patient’s clinical situation and their treatment plan. 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.

“Only some specific clonal haematopoiesis mutations are likely to predict a higher risk of blood cancer developing at some point in the future. This study suggests 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.”

Source: 34th EORTC-NCI-AACR Symposium