Memorial Sloan Kettering Cancer Center (MSK) researchers published new results that found that individuals with low-risk or intermediate-risk myeloma precursor disease known as monoclonal gammopathy of undetermined significance (MGUS) can convert to high-risk MGUS and progress to multiple myeloma within a 5-year window. This research clinically supports recommendations for annual blood tests for all individuals diagnosed with MGUS along with re-assessments of a patient’s clinical-risk status. Their research was published today online in JAMA Oncology.

Bottom line

A team of researchers, co-led by MSK’s C. Ola Landgren, MD, PhD, corresponding author, and chief of MSK’s Myeloma Service, hypothesized that changes in serum immune markers over time predicted progression from MGUS to multiple myeloma. Dr. Landgren and colleagues designed the first prospective study with serial blood samples to investigate blood-based immune markers associated with progression from MGUS to multiple myeloma. Currently, based on existing retrospective studies, risk for multiple myeloma is determined when MGUS is diagnosed. Dr. Landgren and colleagues show that risk can evolve, and low-risk disease can become high-risk and progress to multiple myeloma.

Method and design

Through a unique collaboration with the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian (NCI-PLCO) cancer screening trial, the prospective study followed 77,469 people, ages 55 to 74 years old, who were all cancer free at the time of enrollment. Using serum collection, researchers identified all subjects who developed myeloma and who had stored preceding samples. They studied the changes in serum immune markers year by year. Study participants donated blood samples annually for 19 years (1992 to 2011). All samples were stored at the National Cancer Institute. Researchers obtained all available serially stored serum samples for all these individuals (3,266 samples in total) and conducted cross-sectional and longitudinal analyses of serum markers in relation to progression. Researchers also screened over 6,000 people without myeloma to define MGUS cases.

Findings

Dr. Landgren and his colleagues found that clinical risk categories can change over time prior to multiple myeloma diagnosis. Individuals with low-risk/intermediate-risk MGUS can convert to high-risk MGUS and progress to multiple myeloma within 5 years; the same result was found in light-chain (characterized by absent M-protein) MGUS. These results support the need for annual blood testing and risk assessment for all individuals with MGUS or light-chain MGUS.

Journal

“Association of Immune Marker Changes with Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma," was published online in JAMA Oncology on July 18, 2019.

Expert commentary

“This study, based on prospectively collected samples, helps us to better understand the findings of the prior retrospective studies,” said Dr. Landgren. “Previously reported annual risk of progression from MGUS to multiple myeloma of 0.5% to 1% reflected the average risk among all MGUS cases but were not applicable to individual patients. In the current study, we found that the risk of progression is not constant. Our data indicates that individuals with low-risk or intermediate-risk MGUS can convert to high-risk MGUS and progress to multiple myeloma within a 5-year window. This finding has direct clinical relevance and supports annual blood tests for all individuals diagnosed with MGUS or light-chain MGUS, and, importantly, yearly re-assessment of a patient’s clinical-risk status.”

“We now have insight that shows an individual patient’s risk of progression from MGUS to multiple myeloma is not constant over the years. The same is true for individuals with light-chain MGUS. Based on our new data, we have already expanded our research program on multiple myeloma and its precursor disease to focus on genomic evolution characterization of the bone marrow microenvironment. This will help us further understand biological mechanisms of the development of multiple myeloma.”

Funding

Funding support for this publication was provided by MSK Core Grant P30 CA008748; the Perelman Family Foundation in collaboration with the Multiple Myeloma Research Foundation (MMRF), and the Intramural Research Program of the National Cancer Institute.