Multiple Myeloma Awareness Month: Symptom Recognition and Understanding Precursor Conditions Are Key for Diagnosis

Joshua Richter, MD

Understanding the precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma, along with recognizing hallmark CRAB symptoms—high calcium, renal problems, anemia, and bone lesions—are key to a timely diagnosis of multiple myeloma, according to Joshua Richter, MD.

“In Multiple Myeloma Awareness Month, the key thing [to remember] is that [plasma] disorders are more prevalent than we may think,” Richter said. “If you are a nephrologist, a neurologist, or a primary care doctor, and you have a concern for CRAB-like symptoms, make sure you send that patient for work up so we can see [if multiple myeloma is a possibility].”

In the first part of an interview with OncLive®, Richter delved into the epidemiology and diagnosis of multiple myeloma; the importance of delineating between different plasma disorders to arrive at a correct diagnosis; and how the multiple myeloma treatment paradigm has evolved.

Richter is an associate professor of medicine in the Division of Hematology and Medical Oncology at the Tisch Cancer Institute, as well as director of Multiple Myeloma at the Blavatnik Family-Chelsea Medical Center at Mount Sinai in New York, New York.

OncLive: How would you describe the current understanding of the epidemiology of multiple myeloma?

Richter: I make the analogy of when we were all younger and we got in trouble [at school], and you had to write something on the chalkboard. If I asked you to [write something] one time, you'll write it perfectly. If I asked you to do that 10 times, that final line may not be so good. If I asked you to write it 1 million times, it's just going to [turn into] chicken scratch. Over time, the bone marrow [operates] the same way. The more we [continue] to make new cells, there is a higher chance that there's going to be a problem.

As we get older, there's a higher and higher likelihood of [our bone marrow] making a couple of bad cells. Having an abnormal group of plasma cells—not multiple myeloma, but MGUS—is common. In fact, approximately 2% to 4% of the entire population [over 50 years of age] has [MGUS], and we know that [the prevalence of] myeloma increases with age. The average age [at diagnosis] in the United States [US] is around 69 years, and somewhere between 180,000 and 200,000 people in the US are living with myeloma right now.

We know that all myeloma arises from an earlier state, like MGUS. Acute myeloid leukemia [AML] can be arise from an earlier state, like from myelodysplastic syndromes or myeloproliferative neoplasms, but AML can also be de novo. However, myeloma is never de novo, and we learned this from amazing work that was done at Walter Reed National Military Medical Center. They looked at people diagnosed with myeloma [using] old samples that have been stored, and every single one of them had a precursor disorder, even dating back years or decades for some patients. We know that in an aging population, we're only going to see more and more of these abnormalities. Some need to be treated, and others don't.

What guidance would you offer primary care physicians in identifying early abnormalities that may indicate a possible myeloma diagnosis?

If you want to start thinking about plasma cell problems, there are 2 bits of advice I would give. Anytime we see the CRAB symptoms—high calcium, kidney problems, anemia, or bone lesions—myeloma should be thought of and part of that diagnostic process. For example, if a patient [presents] with anemia but their iron levels are fine, check for a paraprotein. If their calcium level is up, could this be myeloma?

The other thing is that I think [many clinicians] will only consider multiple myeloma or MGUS, and that's not the way it is. There is a lot of middle ground of plasma cell problems that are not myeloma, but they’re also not MGUS; they're in the middle, such as light chain amyloidosis.

When thinking of MGUS, if you find an abnormal protein, that's a diagnosis of exclusion. Therefore, don't just say, ‘It's a monoclonal spike of 0.2 g/dL, it's nothing.’ You can have a monoclonal spike of 0.2 g/dL that's causing amyloidosis, and you can have a monoclonal spike of 3.5 g/dL that is smoldering myeloma and doesn't need treatment.

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

The reality is that there are evolving data about how to treat myeloma and maybe how to prevent [its] evolution. We're likely to see an approval within the year for daratumumab [Darzalex] for smoldering myeloma to prevent progression to symptomatic disease.

The most important thing is the evolution that I've seen in my practice. When I first started, I would sit down and tell people we can't cure the disease. That’s not what I say now. Today, we cure some people by accident. We're going to cure more intentionally with the ultimate goal of curing everyone, and that's going to happen. My job as a physician is to help guide [patients] through that.

For many people, we even provide what we call a functional cure. If you look at some data, and let's take an 80-year-old diagnosed with myeloma. Let’s say you give them upfront isatuximab-irfc [Sarclisa], bortezomib [Velcade], lenalidomide [Revlimid], and dexamethasone [with a] 90 month progression-free survival on average. At first relapse, you give them belantamab mafodotin in combination with pomalidomide [Pomalyst] and dexamethasone, and [this has been associated with a] median PFS of [approximately 36 months]. [Between] 90 months and 36 months, we're getting close to a decade [before the need for third-line treatment] a patient diagnosed at 80 years of age who never has to be admitted to the hospital. That is a functional cure for many of those patients. They will not die of myeloma, rather they will unfortunately with it in remission. A cure, in some version, is in sight for many people.