The first results from the largest screening study yet conducted in the United States of people at high risk for the blood cancer multiple myeloma show that older adults who are Black or who have an immediate family member with a current or past blood cancer have higher rates of multiple myeloma precursor conditions and may benefit from periodic screening and early intervention that might prevent the disease.

“We know that in cancers such as breast cancer and lung cancer, screening, early detection, and early intervention can make a difference in patient survival,” said Irene M. Ghobrial, MD, of the Dana-Farber Cancer Institute in Boston.

“We have shown for the first time that with highly sensitive screening techniques it may eventually be possible to make a difference in the survival of people at elevated risk for multiple myeloma.” 

A precancerous condition called monoclonal gammopathy of undetermined significance (MGUS) carries a 1%-per-year risk of progressing to multiple myeloma.

The defining feature of MGUS is a moderately elevated blood level of protein known as monoclonal, or M protein, which is made by plasma cells, a type of white blood cell. MGUS has no signs or symptoms and currently doctors do not routinely screen patients for it, Dr. Ghobrial said.

A previous study estimated that 3% of Americans ages 50 and older have MGUS, but that study was conducted in people predominantly of European descent.

Although studies have shown that people of African descent and those with a family history of blood cancers are at increased risk for multiple myeloma, no previous study had looked at the prevalence of MGUS in a prospectively followed high-risk population.

The PROMISE study, launched in 2019, aims to enrol 30,000 people ages 40 to 75 who are at above-average risk for multiple myeloma because they are Black or have a parent, sibling, or child with a history of multiple myeloma or another blood cancer.

Study participants provide a blood sample that is tested for MGUS using both conventional and newer high-sensitivity techniques. All PROMISE study participants who test positive for MGUS are referred to a medical specialist in the treatment of blood cancers for further testing and follow-up.

To ensure adequate representation of people of African descent in the study population, Dr. Ghobrial and colleagues also identified and screened Black people who had contributed blood samples to a large biological specimen repository, the Mass General Brigham Biobank in Boston. For this cohort, up to 10 years of follow-up data were available.

In the current study, the investigators report interim screening findings for 7,622 participants, including 2,439 Black people.

“Ours is the largest cohort of Black people to be recruited for a myeloma screening study and the first prospective study to actively recruit people at high risk for multiple myeloma, follow them over time to accurately estimate the prevalence of MGUS, and explore outcomes for patients with this precursor condition,” said Dr. Ghobrial.

“Using screening techniques that are currently available in doctors’ offices, we show that the prevalence of MGUS in a high-risk population over age 50 (Black people and people who have a first-degree relative with a blood cancer) is twice as high as in the general United States population,” she said.

“Using a novel, high-sensitivity screening technique (mass spectrometry), we detected MGUS in 14% of participants. And when we fully employ the capability of mass spectrometry to detect even minute amounts of M-protein in the blood, we can detect the protein in 42% of the high-risk population over age 50.”

When the investigators examined the follow-up data for participants whose samples came from the Biobank, they found that, after a median of 4.5 years of follow-up, those with any level of M-protein had negative health effects, seen as a slightly higher mortality rate from any cause than people who had no M-protein in their blood.

“This suggests that people with M-protein are at risk of not only multiple myeloma but also of other conditions, including other blood cancers and heart attacks,” said Dr. Ghobrial.

“We believe these results make a strong case that older adults who are Black or who have a first-degree relative with a blood cancer could benefit from regular, high-sensitivity screening, and early intervention.”

In the future, Dr. Ghobrial and her research team hope that the PROMISE study will help identify the factors that contribute to the development of MGUS, cause MGUS to progress to overt cancer in some people but not others, and result in negative health effects for people who have any level of M-protein in their blood.

Source: American Society of Haematology