Patients With Low-Risk Multiple Myeloma Precursor Can Progress to the Disease in Just 5 Years

Patients with monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), can progress from low- or intermediate-risk to MM in just 5 years, according to researchers who are now recommending all patients with MGUS undergo blood testing and risk assessment.

All patients who are diagnosed with monoclonal gammopathy of undetermined significance (MGUS) should undergo annual blood testing and risk assessment for developing multiple myeloma (MM), according to a new study in JAMA Oncology.

Researchers with Memorial Sloan Kettering Cancer Center found that patients who have low- or intermediate-risk MGUS, a precursor to MM, can convert to high-risk MGUS and develop MM within just 5 years. MGUS is typically diagnosed during medical workups for other reasons, but research has shown it can start at age 30 and is present in 2.3% of people age 50 years or older.

“This study based on prospectively collected samples helps us to better understand the findings of the prior retrospective studies,” C. Ola Landgren, MD, PhD, explained in a statement. “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.”

The study included 685 people with progressing or stable MGUS. Of these patients, 187 progressed from non—immunoglobulin (Ig) M MGUS to MM and from light-chain MGUS to light-chain MM. However, for 498 patients, the diagnosis remained non-IgM MGUS or light-chain MGUS without progression to MM. The patients were followed for a maximum of 16 years.

Patients who had IgA were more likely to have progressive MGUS (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P&thinsp;=&thinsp;.04), as were patients with skewed serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P&thinsp;<.001), with 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P&thinsp;<.001), and with severe immunoparesis (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P&thinsp;<.001). In addition, patients with skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P&thinsp;<.001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P&thinsp;<.001) were likely to have progressive light-chain MGUS.

In a longitudinal analysis of 43 patients with serial samples prior to progression, the researchers found that 23 (53%) had high-risk MGUS before they progressed. Of those with high-risk MGUS 16 (70%) had converted from low- or intermediate-risk MGUS to MM within 5 years. The findings were similar for light-chain MGUS.

“The findings suggest that individuals with low-risk or intermediate-risk MGUS, including those with light-chain MGUS, can experience progression to high-risk MGUS multiple myeloma within 5 years,” the authors concluded. “Our results may be clinically relevant and support annual blood tests for all individuals diagnosed with MGUS or light-chain MGUS.”


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.

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