Myeloma Precursor Disease Can Start Much Earlier than Expected, Especially in African Americans

A new study suggests that healthcare providers should consider looking for  monoclonal gammopathy of undetermined significance (MGUS) in younger African Americans.

A new study suggests that healthcare providers should consider looking for monoclonal gammopathy of undetermined significance (MGUS) in younger African Americans.

The medical community is always learning more about the hereditary nature of cancer. It’s becoming more apparent that some cancers and cancer-related genetic alterations are more frequent in certain racial and ethnic groups. For example, mutations in the genes BRCA1 and BRCA2 are more common in people of Ashkenazi Jewish descent. And research has indicated that multiple myeloma, a type of blood cancer, occurs more often in African Americans. In addition, this group tends to be younger at the time of the disease’s onset.

Multiple myeloma occurs when plasma cells, a kind of white blood cell, form tumors in the bone marrow. Every year it affects about 30,000 people in the United States. More than 100,000 Americans are currently living with multiple myeloma. The average age of onset is about 70 years old. Fewer than 5% of people with multiple myeloma are diagnosed before age 50.

Previously, a large screening study of more than 77,000 people showed that multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), a condition in which the blood produces an abnormal protein that can be detected with blood tests. A team of researchers from Memorial Sloan Kettering has collaborated with the Mayo Clinic and the National Cancer Institute on a new wide-ranging study that looked for the first signs of MGUS across racial groups. It found that MGUS, like multiple myeloma, appears with higher frequency in African Americans. MGUS also comes on at a much younger average age in African Americans compared with other ethnic groups.

MGUS comes on at a much younger average age in African Americans compared with other ethnic groups.

“By screening blood from 12,372 individuals between ten and 50 years of age, we have re-drawn the map of the myeloma precursor disease MGUS,” says Ola Landgren, Chief of MSK’s Multiple Myeloma Service and lead author of the new study, which is being published in the Nature publication Blood Cancer Journal. “Our results show that MGUS starts with people in their 30s, which is 20 years younger than we used to think.

“It makes sense that MGUS appears more frequently in younger African Americans,” he adds, “since we know that multiple myeloma also occurs at a younger average age in this group. These findings set the agenda for trying to identify these patients, to learn who is going to develop cancer, and to determine whether we can do early intervention to prevent it.“

Taking Advantage of a Wide-Ranging Biobank and Database

To do this analysis, the investigators used data from the National Health and Nutrition Examination Survey (NHANES). This government-funded study has been ongoing since the 1960s. NHANES regularly collects blood samples and health data from adults and children in the United States for a range of research. Dr. Landgren’s team analyzed 12,372 blood samples from that study: about 4,000 from African Americans, 4,000 from Hispanics, 3,600 from whites, and the rest from other ethnic groups. The samples included those from people between the ages of ten and 50. “No prior population-based study has screened for the presence of MGUS in people this young before, so these results are entirely unique,” he says.

The study found that prevalence rates differed substantially across ethnic groups. Starting at age 30, African Americans already had a rate of MGUS that was close to 1%, and by ages 40 to 49, it was 3.3%. By contrast, previous studies have found the rate in whites over age 50 was only about 2%.

“A higher rate of MGUS translates to higher rates of multiple myeloma,” Dr. Landgren explains. “And now we know the early forms of this disease may be lingering for 20 years or more in some people. It’s kind of mind-blowing.”

Dr. Landgren says this study should send an important message to healthcare providers about when to look for these conditions. “Although the majority of people diagnosed with MGUS and multiple myeloma do not have signs until the disease is very advanced, there are some early clues,” he says. “If a younger African American goes to the clinic with symptoms like bone pain, fatigue, or excessive bruising or bleeding, doctors should think about testing him or her for this disease.”

Potential Benefits of Screening

Current guidelines say that people with MGUS should not be treated but should be followed with yearly blood tests. The risk that someone with MGUS will develop multiple myeloma is 0.5 to 1% per year on average. But for people with certain high-risk features, that likelihood can be higher.

Therapies can begin when people first develop smoldering myeloma, another precursor condition to multiple myeloma, which comes after MGUS, rather than waiting for the progression to cancer. Research is under way to determine whether early treatment may provide a benefit. “It’s very possible that in the future, the standard of care will be to initiate treatment earlier in the course of the disease,” Dr. Landgren says. “This change would largely be driven by the development of drugs that have fewer side effects but are still effective, in parallel with better biomarkers to define individuals at a high risk of progression.”

Other ongoing research is investigating the benefits of screening for myeloma precursor diseases in the general population. Dr. Landgren says, “Among people at an increased risk of developing multiple myeloma, such as individuals exposed to Agent Orange or other pesticides and toxins, in my opinion, it seems reasonable to screen for MGUS.”

Improving Diversity in Clinical Research

Dr. Landgren points out that the study’s findings help highlight the importance of including racial minorities in clinical research. “Racial and ethnic disparities in blood cancers are a very understudied area,” he notes. “As the American population becomes more diverse, it’s of major importance that everyone be included in clinical trials. Studies in a number of different cancers have suggested that cancer drugs may not work the same way across all groups.”

MSK’s Cancer Health Equity Research Program, led by gynecologic surgeon Carol Brown, was recently established to address these gaps. “Great advances can have the greatest impact only if diverse groups are included in trials,” she says.

Dr. Landgren adds that although African Americans are at a higher risk of developing multiple myeloma, data show that those who are diagnosed tend to have a less-aggressive disease and better survival rates. “There appear to be differences in the biology of the disease across ethnic groups,” he says. “It clearly warrants further study.”

This research was funded by the National Cancer Institute (under grants CA107476, CA168762, and CA186781).