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Results Point to Annual Assessment of Precursor to Multiple Myeloma

Mary Caffrey
The findings suggest that all patients with monoclonal gammopathy of underdetermined significance should have annual blood testing to monitor whether risk of cancer change over time.
Recent findings from the National Cancer Institute (NCI) show that a benign condition considered a precursor to multiple myeloma can change over time, and the current practice of evaluating a person’s cancer risk just once should change to annual blood tests.1

The plasma cell disorder, called monoclonal gammopathy of underdetermined significance (MGUS), is a premalignant phase that undergoes additional genetic changes before it suddenly develops the growth characteristics seen in multiple myeloma. As the authors note in their study, published in JAMA Oncology, the serum biomarkers that identify MGUS are typically evaluated only during the initial workup; unless a patient is found to be at high risk for multiple myeloma, the markers are not evaluated again.

And that’s a problem, because MGUS evolves over time. Said lead author Ola Landgren, MD, PhD, of professor of medicine and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center, in a statement, “If you’re only going to do one test to determine risk, it’s probably not accurate.”

Instead, the NCI investigators for the first time evaluated serum markers that were prospectively gathered and tracked over time. The study began with 77,469 adults aged 55 to 74 years who were screened from November 1992 to December 2011 as part of the NCI Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. These participants had given researchers blood samples every year for 6 years, and they were tracked to see if they later developed cancer.

All these samples—3266 in all—were obtained and analyzed. Researchers identified 187 patients who developed multiple myeloma who were shown to have progressive MGUS. Another 498 had stable MGUS. They included 461 men (67.3%) with a mean age of 69.1 years.

The investigators found that 23 of the 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) saw their condition convert from low-risk to intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS.1

“The study shows that most of the high-risk patients were low risk at some earlier point,” Landgren said.

As noted in an accompanying editorial, a few of the patients who developed multiple myeloma had low- or intermediate-risk MGUS 1 year prior to developing cancer. This could occur when abnormal plasma cells of these individuals undergo genetic changes that led “to more abrupt progression,” according to the authors of the editorial, led by Nikhil C. Munshi, MD.2

Landgren and coauthors say the findings support “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.”

A large clinical trial in Iceland is screening people 40 years or older for MGUS and examining the benefits and harms of annual blood tests for those found to have the condition. Results are expected in September 2021. NCI is also exploring the use of better biomarkers for multiple myeloma.

Early detection and treatment of multiple myeloma allows patients to receive new combination therapies, which Landgren said can bring “deep, sustained treatment responses,” and no minimal residual disease.

  1. Landgren O, Hofman JN, McShane CM, et al. Association of immune marker changes with progression of monoclonal gammopathy of underdetermined significance to multiple myeloma [published online July 18, 2019]. J Clin Oncol. doi.10.1001/jamaoncol.2019.1568.
  2. Munshi NC, Jagannath S, Avef-Loiseau H. Monoclonal gammopathy may be of unpredictable significance [July 18, 2019]. J Clin Oncol. doi: 10.1001/jamaoncol.2019.1580.

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