Risk of MGUS Progression in Multiple Myeloma Examined

Yearly blood testing and risk assessment for all patients with monoclonal gammopathy of undetermined significance (MGUS) or light-chain MGUS may be clinically prudent, according to the results of a study published in JAMA Oncology.

“The study shows that most of the high-risk patients were low risk at some earlier point,” said lead author Ola Landgren, MD, PhD, Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York in a press release. “So, if you’re only going to do one test to determine risk, it’s probably not accurate.”

The current prospective cross-sectional cohort study analyzed 685 adult participants (mean age 69.1 years; 67.3% men) mined from the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial from 1993 to 2011. Researchers obtained all available serially stored prediagnostic serum samples for each patient totaling 3,266 specimens.

Through 16 years or fewer of follow-up, 187 patients with progression from non-IgM MGUS to multiple myeloma and from light-chain MGUS to light-chain multiple myeloma were identified. Furthermore, 498 patients whose diagnosis remained non-IgM MGUS without progression and light-chain MGUS without progression to multiple myeloma were identified.

Based on a longitudinal analysis of individuals with serial samples predating progression, 23 of 43 patients (53%) had high-risk MGUS before progression, with 16 of these 23 patients (70%) experiencing conversion from low- or intermediate-risk MGUS to multiple myeloma within 5 years. Notably, similar results were observed with light-chain MGUS. Evolving monoclonal proteins, serum-free light chains, and immunosuppression predicted disease progression.

“We provided novel insights by showing that an individual’s risk of progression from MGUS to multiple myeloma was not constant, and the same was true for individuals with light-chain MGUS,” wrote the authors. “This study based on prospectively collected samples may provide better understanding of the findings of previous retrospective follow-up studies.”

Per the literature, the annual risk of progression from MGUS to multiple myeloma has historically been documented as 0.5% to 1.0%. However, this statistic reflecting the mean risk among all MGUS cases, but not risk among individual patients.

When individual markers were combined into a risk score for progression, 53% of patients with progressing MGUS vs 1 of 108 patients with nonprogressing MGUS had a high risk score.

Utilizing serum markers drawn before formal diagnosis of multiple myeloma, the team discovered that only 21% of patients with MGUS progression met the blood-based criteria for smoldering multiple myeloma, and 14% met the criteria for multiple myeloma. In patients with light-chain MGUS progression, 60% met the blood-based criteria for light-chain multiple myeloma before formal diagnosis.

Blood-based criteria were identifiable up to 5 years before formal diagnosis of both multiple myeloma and light-chain multiple myeloma. Nonetheless, the investigators lacked access to bone marrow biopsy results. Consequently, it was impossible to assess data on plasma cell percentage.

Experts hypothesize that the host’s biologic features moderate the regulation of stable precursor disease vs progression. In the current analysis, immunosuppression was noted in 58% of patients with MGUS progression vs 20% of those without MGUS progression. In patients with light-chain MGUS, immunosuppression was observed in 54% of those with disease progression vs 12% of those without progression.

“Future studies should investigate biologic interactions between nontumor and tumor cells in association with progression,” suggested the researchers.