Individuals at high risk for multiple myeloma may benefit from novel screening technique
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A novel high-sensitivity screening approach led to detection of monoclonal gammopathy of undetermined significance at significantly higher rates than conventional methods among people at high risk for multiple myeloma, study results showed.
The findings, presented at ASH Annual Meeting and Exposition, confirmed a high prevalence of the multiple myeloma precursor condition among older adults and individuals who are Black or have a first-degree relative with hematologic malignancy. These individuals may benefit from precision screening methods that enable early detection and clinical intervention, according to researchers.
“For multiple myeloma, screening remains excluded from routine clinical practice today,” Habib El-Khoury, MD, postdoctoral research fellow at Dana-Farber Cancer Institute, told Healio. “Among the reasons behind this [study] is the need to better identify populations at high risk for disease, among whom the benefits of screening would outweigh any potential risk.”
Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma, El-Khoury said. It has been detected in about 3% of individuals aged 50 years and older in a general population that consisted mostly of individuals of European ancestry.
“The purpose of the PROMISE study, launched in 2019, was to better understand the potential benefits of screening in a racially diverse, high-risk U.S. population that is followed prospectively and answer other questions currently under investigation, such as the best method for screening, genetic factors that would predispose to disease and how those interact with environmental factors to increase the risk for disease in certain individuals, familial clustering of disease and others.”
At ASH, researchers reported interim screening results of 7,622 study participants from different age classes, including 2,439 Black individuals and 3,866 non-Black individuals with a family history of hematologic malignancies, who provided blood samples for testing. The rest of the participants underwent screening as controls for risk in the setting of testing the matrix-assisted laser desorption ionization-time of flight mass spectrometry.
“We refer to this method as the Exent MALDI-TOF MS (The Binding Site Group Ltd.),” El-Khoury said. “This novel, higher-sensitivity testing approach allows for the detection of monoclonal proteins (byproduct of plasma cells, which are the cancerous cells in multiple myeloma). To date, most widely available testing methods rely on gel-based electrophoretic assays. The mass spectrometry assay uses sort of the same scientific rationale of identifying monoclonal proteins based on mass to charge to detect, characterize and quantify monoclonal proteins, with a higher sensitivity compared with conventional assays currently used.”
Participants who tested positive for MGUS were referred to a hematologist for additional testing and follow-up and invited to complete epidemiologic exposure and psychosocial questionaries periodically.
Results showed significantly higher rates of MGUS compared with that detected by conventional methods, including serum protein electrophoresis and serum immunofixation tests. Researchers observed the higher rates “while still limiting observations to the lowest limit of detection identified for the conventional methods — 13% vs. 6%, in those at high-risk aged older than 50 years,” El-Khoury told Healio. “Rates of MGUS in our defined high-risk population, detected by either method, were as expected — higher than those reported in the general population aged older than 50 years.”
The higher-sensitivity mass spectrometry assay also enabled researchers to detect lower-level monoclonal gammopathies that the researchers termed monoclonal gammopathies of indeterminate potential (MGIP), El-Khoury said.
“MGIP was detected in around 28% of individuals aged 50 years and older and did not seem to differ by risk classification for myeloma,” he said. “Those remaining lower-level monoclonal gammopathies were seen to increase significantly with aging and showed a distinct biology compared with the known MGUS in terms of the most common isotype of protein and their persistence with time.”
Researchers also found significant associations of MGUS detected by mass spectrometry and the higher concentration proteins within MGIP with decreased OS due to all-cause mortality. These associations were evident among those aged 50 to 64 years at screening (MGIP: HR = 1.57; 95% CI, 0.85-2.92; MGUS: HR = 4.41; 95% CI, 2.45-7.94) and those aged 65 years and older at screening (MGIP: HR = 1.61; 95% CI, 1.03-2.51; MGUS: HR = 2.06; 95% CI, 1.24-3.44).
“The fate of MGIP remains under investigation and the clinical associations we saw with survival and other comorbidities will encourage future studies,” El-Khoury said.
Early data on cancer worry and quality of life suggested a likely minimal psychosocial burden of screening among this population.
Although the PROMISE study has shown the potential benefits of routine, high-sensitivity screening for high-risk populations — including older adults who are Black or have a first-degree relative who has blood cancer — it has yet to answer questions regarding genetic predisposition to disease among these individuals, interaction with environmental factors, and genetic factors behind familial clustering of disease, according to El-Khoury.
“In fact, the PROMISE study was curated to recruit a large number of families with high-prevalence of disease to further explore what might explain such disease clustering,” he said. “The capture of this significantly larger pool of patients with MGUS detected by mass spectrometry will allow us to answer more questions ranging from disease etiology to progression to more advanced stages of smoldering multiple myeloma and multiple myeloma.”
For more information:
Habib El-Khoury, MD, can be reached at habibg_el-khoury@dfci.harvard.edu.
Perspective
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Iberia Romina Sosa, MD, PhD
El Khoury and colleagues reported initial results of PROMISE, the first nationwide U.S. screening study for individuals at high risk for multiple myeloma to better identify the population at risk. Interestingly, despite high risk for multiple myeloma among African Americans, there is no existing descriptive study of the prevalence of MGUS, a premalignant phase, in this specific population.
The study prescreened patients aged 40 years or older who were deemed eligible for screening based on ethnicity and having a first-degree relative with hematologic malignancy. In addition to routine myeloma labs, higher sensitivity MALDI-TOF testing was employed. Unsurprisingly, the results confirmed a high prevalence of MGUS in this at-risk population and provided preliminary evidence for the benefit of precision screening approaches. Moreover, the results showed no significant change in cancer worry among participants who screened positive.
This study is a necessary tool to bridge health equity in the African American population, which often suffers from lack of early intervention. Importantly, the study also showed that the intervention is not psychologically detrimental. I look forward to the full report examining the potential role of socioeconomic factors in this at-risk population.
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El-Khoury H, et al. Abstract 152. Presented at: ASH Annual Meeting and Exposition. Dec. 11-14, 2021; Atlanta.
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