Multiple Myeloma Awareness Month: MGUS Recognition, Symptom Evaluation Drive Diagnosis

Jeffrey Zonder, MD

Identifying monoclonal gammopathy of undetermined significance (MGUS) as a precursor to multiple myeloma and remaining vigilant when assessing nonspecific yet frequent symptoms—such as anemia of unclear origin, unexplained renal impairment, or chronic bone pain—can facilitate earlier diagnosis, particularly among individuals at elevated risk, according to Jeffrey Zonder, MD.

“The fact is, particularly in the communities most affected by multiple myeloma, we need to keep working to [improve] awareness of the disease,” Zonder explained.

In an interview with OncLive®, Zonder discussed epidemiologic trends of multiple myeloma, highlighting the increased prevalence among older adults and individuals of African ancestry. He noted the potential for early identification of MGUS in these groups through routine bloodwork, as well as emerging data from screening efforts like the observational PROMISE study (NCT03689595). He also emphasized that continued therapeutic advancements in myeloma may also benefit patients with related plasma-cell disorders such as amyloidosis.

Zonder is a professor in the Department of Oncology at Wayne State University School of Medicine and a member of the Hematology and Oncology Multidisciplinary Team at Karmanos Cancer Institute in Detroit, Michigan.

OncLive: What are some key aspects of multiple myeloma that deserve greater attention in 2025?

Zonder: Multiple myeloma is an incredibly underappreciated disease. A lot of people have never heard of multiple myeloma until the day they're diagnosed, or when they're being worked up for the possibility of diagnosis. This has changed a little bit over time. People are living a lot longer with myeloma now than they did in the past; therefore, the number of people walking around with multiple myeloma is higher than it's ever been. People are more likely to know somebody who has myeloma, but particularly [for] communities most affected by multiple myeloma, we need to keep working on awareness of the disease.

Which patient populations or communities are at higher risk for developing multiple myeloma?

[Multiple myeloma] is an age-related condition, and there is also a difference in the prevalence according to race and ethnicity.

The frequency of this disease is highest in the non-Hispanic Black population in the United States; the likelihood of being diagnosed with multiple myeloma is approximately twice as high in non-Hispanic Black people [compared with] the [overall] population.

[This disparity] may stem from a higher incidence of the precursor condition, MGUS. All cases of myeloma arise from MGUS. MGUS, by definition, is an asymptomatic condition, so it's usually picked up on blood work. [Often times, a provider] notices that somebody's protein levels [are] too high or that their antibody levels seem too low. They end up getting additional blood work that leads to a diagnosis [of MGUS]. A higher risk of MGUS leads to a higher risk of myeloma in older people and in Black people compared with other populations.

What clinical symptoms help inform a multiple myeloma diagnosis?

Sometimes, simple lab work is the clue. [When a patient presents with] unexplained anemia without any other obvious cause, unexplained kidney problems without any other obvious cause, or new bone pain, [myeloma should be considered]. The problem is that these types of symptoms are pretty common.

Anemia is a common medical condition seen in a primary care physician's office, [and the same can be said for] back pain, particularly in the [older] demographic that we're talking about. The incidence of myeloma goes up as we get older, and the median age of diagnosis is a little over 70 [years; for this demographic,] back pain is common. Therefore, there is no specific patient population for whom we're [currently] recommending screening.

There are ongoing studies like the [observational] PROMISE study that are looking at this exact question by doing blood work to determine the frequency or the likelihood of myeloma [developing] in particularly for high-risk patients. In [PROMISE], patients who are over 30 [years of age] and are African American or have a first-degree relative [who was diagnosed with a blood cancer] can have blood work collected and be screened for myeloma or the precursor condition MGUS.

Already, the very earliest results on this study show us that when you screen those specified populations, the instance of MGUS or some other plasma-cell disorder is above 10%, and that includes some patients who are not 60, 70, or 80 [years of age]. Like I said, 30-year-old patients can be eligible for that screening, so we may be heading into an era when we where we identify populations that could benefit from screening.

They are also willing to enroll patients as young as 18 if they have 2 first-degree relatives who have [a blood cancer]. That’s not going to be a big slice of the study, but we might learn something about familial risk. We don't think of myeloma as a familial disease, except that we know that first-degree family members do have a slightly increased risk of [developing] myeloma, lymphoma, or related conditions. All myeloma or amyloid specialists have families in our practice with multiple affected members. I can think of several families in my own practice with 2 or 3 affected members.

What key message would you like to share with colleagues in recognition of Multiple Myeloma Awareness Month?

We still think of myeloma as an incurable cancer for most patients, but therapy is better now than it's ever been, and we've made gains in all patient subsets. We're doing better with high-risk disease, and we're doing particularly better with standard-risk disease.

We've made a lot of gains in the last couple of years; we've had randomized trials that show that the aggressive 4-drug regimens that we use as induction therapy for younger patients are helpful in older patients. We're making gains there, and we're just now getting to the point where there are some patients who have disease control that is good enough, instead of continuously adding more and more to regimens and adding more and more months to maintenance.

We're also getting to a point where we're trying to identify patients in whom we could pull back on therapy a little bit because they've done so well for so long on traditional therapy. We [don’t want] therapy to be endless for everybody, and we're making a lot of progress on that.

During Multiple Myeloma Awareness Month, we should also be aware of amyloidosis, which is a different plasma-cell disease. The therapies that we use to treat amyloidosis are all therapies that we have developed for multiple myeloma, and it's a tricky disease to treat. The patients are very fragile, and it's approximately [20%] as common as myeloma; however, it's important to remember, as we keep pushing the envelope in myeloma, there is another potential new therapy in amyloidosis. We have to do the studies to see how to use them effectively in amyloidosis.

I'd encourage clinicians to remember when they see a patient with MGUS to not just ask about back pain and check their calcium level; make sure you ask about peripheral neuropathy and about symptoms of congestive heart failure. Also, make sure to look for evidence of heavy protein loss in the urine because those symptoms could be the red flag symptoms for amyloidosis rather than multiple myeloma, and we wouldn’t want to assume a patient has MGUS just because they don't quite meet the criteria for having a diagnosis of myeloma [when they may have] this rarer but also potentially fatal disease, amyloidosis.