New Data Contradict Previous Ideas About MGUS Risk Status

August 9, 2019

New data push back against previous thinking that an individual's risk of progression from MGUS to multiple myeloma was constant.

New data published in JAMA Oncology suggest that low-risk or intermediate-risk monoclonal gammopathy of unknown significance (MGUS) can convert to high-risk MGUS and progress to multiple myeloma within 5 years. These data are in contrast to previous thinking that suggested that an individual’s risk of progression from MGUS to multiple myeloma was constant.

“This finding is clinically relevant and supports annual blood testing for all individuals diagnosed with MGUS or light-chain MGUS, as well as yearly assessment of a patient’s clinical risk status,” Ola Landgren, MD, PhD, of Memorial Sloan Kettering Cancer Center, and colleagues wrote in JAMA Oncology.

The study used data from the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial that included 187 patients with progressing MGUS and 498 with stable MGUS, including light-chain subtype. Data were from November 1993 to December 2011.

Using cross-sectional modeling, Landgren and colleagues identified several risk factors associated with progressive MGUS: IgA isotype (adjusted odds ratio=1.80; 95% CI, 1.03–3.13; P=.04), 15 g/L or more monoclonal spike (aOR=23.5; 95% CI, 8.9–61.9; P<.001), skewed serum free light chains ratio (aOR=46.4; 95% CI, 18.4–117.0; P<.001), and severe immunoparesis (adOR=19.1; 95% CI, 7.5–48.3; P<.001).

Those factors associated with progressive light-chain MGUS were skewed free light chains ratio (aOR-44.0; 95% CI, 14.2–136.3; P<.001) and severe immunoparesis (aOR=48.6; 95% CI, 9.5–248.2; P<.001).

Among those patients with serial blood samples taken prior to disease progression, more than half (53%) had high-risk MGUS before progression. Of those with high risk, 70% had a conversion from low-risk or intermediate-risk MGUS within the prior 5 years. Among patients with light-chain MGUS who had high-risk status before multiple myeloma diagnosis, 71% had prior blood samples showing low-risk or intermediate-risk scores.

In an accompanying editorial, Nikhil C. Munshi, MD, of Dana-Farber Cancer Institute, and colleagues wrote that if the findings by Landgren et al. are confirmed in other studies, “it would require rethinking of our strategy to follow these patients, as well as development of strategies to prevent progression, not only in high-risk patients, but also in patients at intermediate to low risk of progression.”

“This study by Landgren et al. provides an important and biologically relevant concept that risk features are not stagnant, and that patients with MGUS may evolve over time, with the disease developing more aggressive characteristics prior to proceeding to developing malignant transformation,” Munshi and colleagues wrote. “An ongoing question would be: can we identify those patients in each of the risk categories who have extremely low chance of progression? In this regard, studying the patients’ genomics, especially the ability to evolve over time, may be critical in understanding this biological transformation with significant implications for therapy and patient treatment.”