Monoclonal gammopathy of undetermined significance (MGUS) is a noncancerous condition in which plasma cells release an abnormal protein into the blood. For many people living with MGUS, their biggest concern is that the condition will evolve into multiple myeloma, a type of blood cancer.

There is no proven way to prevent the progression of MGUS into multiple myeloma. However, researchers are testing new treatments to slow or stop its progression to multiple myeloma.

Monitoring and Follow-Ups

MGUS is a benign (not harmful) condition and rarely causes symptoms. Doctors generally do not offer any kind of treatment for people who have it. Instead, doctors will monitor for any signs that a person’s condition might be progressing.

Generally, a doctor will use blood tests to assess the risk of progression. These tests can evaluate the type and amount of abnormal protein in a person’s blood. For people with MGUS who are considered low-risk, follow-ups may be unnecessary, or a doctor may recommend these appointments happen every 12 months. Follow-ups are more frequent for those considered high-risk. This way, if the condition progresses, it can be caught early and treated immediately.

Specialty Treatment and Research Centers

Some hospitals have specialty centers that bring together research, clinical trials, and clinical management of MGUS and smoldering multiple myeloma (SMM), both of which are considered multiple myeloma precursor conditions. People with SMM have higher levels of plasma cells and M protein (an abnormal antibody associated with myeloma) than people with MGUS, but lower levels than people with multiple myeloma.

Examples of these specialty clinics include:

• Center of Excellence for Multiple Myeloma and Multiple Myeloma Precursor Clinic at Mount Sinai Tisch Cancer Center, located in New York
• Center for Prevention of Progression at Dana-Farber Cancer Institute, located in Boston
• MGUS Clinic at Penn State Cancer Institute in Hershey, Pennsylvania

Additionally, City of Hope, based in Duarte, California, has a designated myeloma and multiple myeloma care team.

Whether or not you attend a specialty clinic, be honest with your health care team about your symptoms, concerns, and plans. Your health team can discuss the risks and benefits of possible preventive measures.

Clinical Studies for Preventing Progression

Treating multiple myeloma is difficult. Doctors and scientists hope to find ways to prevent MGUS from evolving into multiple myeloma. Clinical trials — research studies evaluating treatment effectiveness on people — are underway to test prescription medications and lifestyle interventions. You may qualify to join a clinical study on MGUS. If you’re interested in participating in research, visit Clinicaltrials.gov or ask your doctor about opportunities for which you may qualify.

Following are several treatments being studied in clinical trials.

CD38 Antibody Daratumumab

Daratumumab (Darzalex) is currently approved by the U.S. Food and Drug Administration (FDA) for treating multiple myeloma. The drug is a monoclonal antibody that targets CD38, a molecule that is found more on the surface of myeloma cells than on healthy cells.

This trial, launched in 2017, includes adults with MGUS or smoldering myeloma who are receiving intravenous (IV) infusions of daratumumab. Doctors will monitor safety and side effects as well as track how many people (if any) progress to multiple myeloma during the trial. It is expected to be completed in 2023.

Dendritic Cell DKK1 Vaccine

An early-stage trial of the Dendritic Cell DKK1 vaccine launched in 2018. It includes adults with monoclonal gammopathies (MGUS and similar conditions). Participants receive three doses of an investigational vaccine, administered two weeks apart. Eleven months of observation follow.

The vaccine contains dendritic cells, a type of immune cell that can activate your immune system. The dendritic cells in the vaccine are collected from a participant’s blood and grown in a lab where they are adapted to recognize DKK1. DKK1 is a protein found on the surface of myeloma cells, but usually not on healthy cells. The vaccine introduces these altered dendritic cells into the blood. There, they can “teach” a person’s immune system to recognize, attack, and kill the myeloma cells.

This trial is intended only to test the safety and side effects of the vaccine and is expected to be completed in 2023.

Rifaximin

Rifaximin (Xifaxan) is an antibiotic. A trial of the drug, launched in 2019, includes adults with monoclonal gammopathies who will take a two-week course of antibiotic pills. It is expected to be completed in late 2022.

This trial is designed to test the safety and side effects of the antibiotic and look for changes in intestinal bacteria. It also entails checking whether the antibiotic affects the number of abnormal proteins or plasma cells a participant has.

Metformin

Metformin (Glucophage XR) is a drug typically used to treat type 2 diabetes, but it is also being used or studied for use to treat many other conditions. This trial, launched in 2021, includes adults with MGUS or smoldering myeloma who will take metformin for six months.

Doctors will monitor safety and side effects. They will also compare whether metformin affects disease progression. The trial is expected to be completed in 2024.

Lifestyle Changes for Preventing Progression

Other studies are investigating how diet and lifestyle changes may help lower the risk of progression.

Curcumin Supplements

Curcumin is a component of turmeric (a spice). A small trial conducted in 2010 found that curcumin could slow the progression of precursor conditions. In the study, participants were randomly assigned to take curcumin or a placebo. Researchers found that curcumin therapy decreased markers of MGUS severity.

Another study launched in 2021 will explore whether curcumin, supplemented with piperine — an alkaloid in black pepper — can prevent or delay the progress of MGUS or SMM. The study is expected to be complete in 2023.

However, there is not yet enough evidence to suggest that people with MGUS should take curcumin supplements. Before starting a new supplement, you should also speak with your health care provider.

Obesity, Diets, and Weight Management

One study, published in 2018, found that eating fruit at least three times per week was associated with lower risks of MGUS diagnosis or progression.

Another study, published in 2017, found that being overweight or obese was a risk factor for progression from MGUS to multiple myeloma.

A trial launched in 2021 was designed to provide a whole-food, plant-based diet for 12 weeks to overweight or obese adults with MGUS or smoldering myeloma. Doctors would then monitor participants’ weight loss and ability to stick to the diet, as well as clinical markers of MGUS and myeloma. The trial is expected to be completed in 2023.

Studies on MGUS Progression

Scientists don't yet understand how and why disease progression occurs. The following research studies are working to learn more about the basic biology of MGUS:

• The IMPACT Study is investigating how the COVID-19 virus and COVID-19 vaccines affect the immune system in people with blood cancer precursor conditions like MGUS.
• The PCROWD Study collects tissue samples from people diagnosed with precursor conditions like MGUS to understand the biological mechanisms of progression.
• The PROMISE Study is gathering data to establish a risk-screening method and to better understand why some people progress to myeloma and others don’t.
• The iStopMM Project is an Icelandic nationwide screening program for multiple myeloma and its precursors.

Talk to Your Doctor

If you want to try improving your overall health through changes to your diet or adding supplements, you don’t need a prescription. However, you should always speak to your health care team before you make adjustments to your treatment plan or supplement regimen. You can also ask whether any new prescription medications have recently become available.

Get Support From Others Who Understand

On MyMyelomaTeam, you’ll meet other people with monoclonal gammopathies. Here, more than 16,000 members who understand life with myeloma come together to share support, advice, and stories from their daily lives.

Do you take steps to try and prevent the progression of MGUS? Share your experiences and thoughts in the comments below or by posting to your Activities feed.