Screening Initiative Identifies Those at Highest Risk of Developing MM

Older Black adults or those who have a first-degree relative with a hematologic malignancy (HM) have a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) and subsequent risk of developing multiple myeloma (MM), according to interim data from the PROMISE study presented at the 2021 American Society of Hematology Annual Meeting and Exposition.

MGUS, a clinically detectable but asymptomatic premalignant phase, has a 1% per-year risk of progression to MM. Thus, the at-risk individuals identified may benefit from precision screening approaches to allow for early detection and clinical intervention, researchers wrote.

According to previous research, approximately 3% of individuals 50 years and older and of European descent have an MGUS, although doctors do not routinely screen for it.

In an effort to better understand the prevalence of MGUS in those at high risk of MM and to characterize clinical variables in those who screen positive, researchers launched a US screening study in 2019 (PROMISE).

All individuals screened are 40 years or older, and those considered at high risk are Black and those with a first-degree relative diagnosed with an HM.

Researchers analyzed participants’ blood, and those who tested positive for MGUS were referred for a clinical follow-up with a hematologist and invited to complete questionnaires as part of the study. In addition, “to enrich the PROMISE cohort with Black individuals, we identified and screened 1868 Black additional individuals from the Mass General Brigham (MGB) Biobank who met the PROMISE enrollment criteria,” researchers added.

Analyses revealed the following:

• Heavy-chain (HC)–MGUS was found in 9.6% (95% CI, 8.6%-11%) of the cohort, with a prevalence of 10% (95% CI, 8.3-12%) in the PROMISE cohort and 9.4% (95% CI, 8.1%-11%) in the MGB cohort.
• HC-MGUS prevalence increased with age in high-risk individuals from 4.9% (95% CI, 3.3%-6.9%) for participants aged 40 to 49 years to 13% (95% CI, 10-17%) for those aged 70 to 79 years (P < 1.2E^-5).
• Among monoclonal HC-MGUS, researchers found 65% IgG, 18% IgM, and 18% IgA.
• M-spike was quantified in 97% of samples.
• Median M-spike concentration was 0.058 g/dL (max, 2.6 g/dL) for IgG, 0.0043 g/dL (max, 0.6 g/dL) for IgM, and 0.067 g/dL (max, 0.8 g/dL) for IgA.

Participants also completed a 4-item cancer worry questionnaire and the RAND 36-item Short Form Survey (SF-36). Across the pre- and postscreening interval, participants who screened positive reported no significant change in cancer worry. On all the 8 subscales assessed, health-related quality of life measured via the SF-36 was also not significantly different in screen-positive vs screen-negative individuals.

“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 coauthor 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.”

The PROMISE study is the largest screening study of its kind and aims to enroll 30,000 individuals at an above-average risk of MM. Researchers hope to use the data collected to investigate factors that contribute to MGUS development and study what causes the condition to progress to cancer in some individuals and not others.

“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,” Ghobrial said.

Reference

El-Khoury H, Alberge J, Barr H, et al. High prevalence of monoclonal gammopathy in a population at risk: the first results of the promise study. Presented at: 63rd Annual American Society of Hematology Meeting and Exposition. Abstract 152. Accessed January 17, 2022. https://ash.confex.com/ash/2021/webprogram/Paper149868.html