The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
