In a second long-term assessment, the researchers reported that “in longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression, and 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years; similar results were found for light-chain MGUS.”

These data, in particular, were most intriguing to Dr Landgren. “The risk signature is not constant in a given patient over time,” she said. “Low-risk can stay low-risk, but it can also convert into intermediate- or high-risk. Risk signatures can change.”

Dr Hoffman says that these data have direct clinical relevance for monitoring patients’ risk for progression of MGUS to MM. “Our findings support annual monitoring and blood testing for MGUS patients, and yearly reassessment of a patient’s risk of progression to multiple myeloma.”

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But, what exactly would annual monitoring look like? Dr Landgren suggested something radical: “Getting rid of ‘undetermined significance’ by splitting MGUS into (1) monoclonal gammopathy, and (2) early myeloma.”


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Doing this will help identify patients who are at low risk for progression and those who could benefit from robust monitoring, she said. In addition, it would help determine which individuals would benefit from early treatment. “This is what patients are asking about. They want to know their individual risk signature, not the average risk. With modern genomic technologies, it is possible to reach much further,” noted Dr Landgren.

Genomics is an area of ongoing study for Dr Landgren. Her research program is currently analyzing bone marrow biopsies/aspirates of people with MGUS on an annual basis to detect changes in blood markers and to define genomic markers of progression by sequencing precursor cells. She and colleagues are also performing genomic profiling of the bone marrow microenvironment.

“We are already far along with these studies, and we have started to identify signatures associated with progression,” she says. “This work has great potential and could dramatically change clinical counseling given that it could offer early identification of treatment candidates.”

Reference

Landgren O, Hofmann JN, McShane CM, et al. Association of immune marker changes with progression of monoclonal gammopathy of undetermined significance to multiple myeloma [published online July 18, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.1568