Multiple Myeloma: What Every Oncology APP Needs to Know

Key Takeaways

• Oncology APPs should recognize that multiple myeloma may be diagnosed without classic CRAB findings and that evaluation incorporates myeloma-specific laboratory studies, bone marrow assessment, imaging, and cytogenetic risk stratification.
• Myeloma care is a continuum of treatment in which APPs help patients navigate individualized initial therapy, transplant considerations, maintenance, and evolving relapse therapies, including CAR T-cell therapy and bispecific antibodies.
• APPs should interpret laboratory trends alongside symptoms, disease biology, and prior treatment responses to recognize progression, manage toxicities, educate patients and caregivers, and coordinate care.

Donna Catamero, ANP-BC, OCN, CCRC, a nurse practitioner at Mount Sinai Medical Center in New York City, reviews the diagnosis, treatment, and longitudinal management of multiple myeloma for oncology APPs. She discusses CRAB and SLiM-CRAB criteria, cytogenetic risk assessment, quadruplet therapy, transplant eligibility, maintenance, and the expanding role of CAR T-cell therapy and bispecific antibodies. Emphasizing that myeloma care extends across multiple lines of treatment, Catamero highlights the importance of interpreting laboratory trends alongside symptoms, disease biology, and treatment history to support earlier recognition of progression, effective toxicity management, and coordinated care.

Transcript

Hello, my name is Donna Catamero. I’m a nurse practitioner at the Mount Sinai School of Medicine in New York City. 

I first want to start off with a very simple definition of what multiple myeloma is. It’s a malignancy of plasma cells, and our plasma cells, as we know, produce our antibodies. They live in the bone marrow. It’s a heterogeneous disease. Patients can present with both different factors of how they present with biology and then how they present symptomatically. And the prognosis can be different, varying with what type of disease the patient has.

I think, in terms of how a patient presents, many APPs are very familiar with CRAB features: hypercalcemia, renal dysfunction, anemia, and bone disease. But patients don’t always present with these findings. And presentation might include fatigue or pain, recurrent infections, because, again, it’s a disease of the plasma cells. We often see neuropathies. And then we look at the patient’s blood count. We can see elevations in a patient’s protein level. We can see anemia, and we can see a monoclonal protein.

How do we work a patient up? Generally, how we find myeloma is doing a CBC and a comprehensive metabolic panel. And we can see the anemia; we can see renal function. But then we have more specific myeloma tests: serum protein electrophoresis with immunofixation. We look at the immunoglobulins, serum free light chains, and other urine studies. And this gives us a sense of what the disease looks like.

We also will do a bone marrow biopsy, and this is really definitive for diagnosis. And this establishes the extent of disease, how many of those clonal plasma cells are in the bone marrow. And then we’ll also do some imaging studies for patients: either a low-dose whole-body CT, PET/CTs, or MRI. And here we’re looking for bone disease or any extramedullary disease.

And it’s important. A good, I think, teaching point is myeloma does not always present as your typical CRAB or end-organ damage. We recently incorporated what we call SLiM-CRAB. Yes, we have the symptomatic hypercalcemia and the renal dysfunction, but we’re also looking at high risk for disease progression.

We look at that bone marrow, and we look to see if there’s over 60% of plasma cells in that bone marrow. We look at the free light chain, with the involved-to-uninvolved ratio being over 100. We look at focal lesions on MRI. If we have any of those SLiM criteria, patients will be diagnosed with myeloma regardless of the CRAB symptoms.

Next, we’ll look at risk assessment, and for this we incorporate cytogenetics and fluorescence in situ hybridization (FISH). There are some features, high-risk cytogenetics, that we can identify in patients that may have more aggressive disease, and this is going to require us to really monitor these patients very closely. They might not respond for as long a duration to therapy as those with standard-risk disease.

I just want to emphasize that risk is dynamic. Yes, we do look at biology and cytogenetics, but there’s also the clinical behavior of myeloma, and that can change over time, particularly with each relapse.

Treatment in myeloma—we can’t look at it as a single regimen. It’s a continuum of therapy. And for the most part, we say that myeloma is treatable, not curable, but I would say it might be someday soon that we’re talking about curable disease. But we have to frame it as our patients are going to receive multiple lines of therapy over many years.

And when someone is newly diagnosed, we do our initial line of therapy, and we’re going to incorporate a combination of drugs. Typically, the new standard is a combination of 4 drug classes, and that includes proteasome inhibitors, immunomodulatory agents, corticosteroids, and a CD38-directed monoclonal antibody. And then we’ll titrate dosing and schedule according to a patient’s age, frailty, other comorbidities. But now really, again, the standard of care is to do a combination of 4 drugs.

And then we look at transplant eligibility. It’s easy to think in terms of age—is someone over 70 or under 70—if they’re transplant eligible, but we want to really think about it as based on fitness, comorbidities, functional status, and, of course, patient preference. Patients will have several cycles of their initial therapy. We’ll collect stem cells, followed by high-dose melphalan with a stem cell rescue.

And then after this, patients will go into maintenance therapy. And this is to deepen and sustain the response of that initial therapy, with or without transplant. And new data are emerging that, for patients who have standard-risk cytogenetics, there may be a fixed duration of maintenance so that patients are not on therapy for prolonged periods of time. Of course, patients who have high-risk cytogenetics, we have to monitor those patients very closely, and they might be on a 1- or 2-drug maintenance regimen.

But like I said, this is a treatable disease, and patients are going to require multiple lines of therapy. With this 4-drug regimen, we can keep patients in remission for many years, but we do anticipate patients to relapse. And I think the exciting thing in the myeloma field right now is that we have many exciting options in that early-relapse setting.

In fact, it’s still evolving. We have CAR T-cell therapies, bispecific therapies, and they’re moving into earlier lines. And eventually, we’ll actually probably see these therapies in newly diagnosed patients. But for now, they’re available after 1 line of therapy. And now we’re seeing really deep and durable remissions. Again, even with a second line of therapy, we’re keeping patients in remission for years.

Monitoring patients—I think this is really a crucial role for our advanced practice providers, and I think this is where we really excel. We monitor our patients through that continuum of treatment, and we don’t monitor myeloma-specific blood work in isolation.

For example, we don’t look at that M-spike in isolation. We’re looking at all of the patient’s labs. Yes, the M-spike, but also serum free light chains, immunoglobulins at the same time. We’re looking at CBC, renal function, and other chemistries. And we’re not looking at 1 time point. We’re looking at trends over time.

And we’re trying to understand our patient’s myeloma, the cytogenetics, how it’s going to behave, how a patient did in previous relapses. And we’re all taking that into consideration when we’re monitoring patients.

But there are some clinical red flags that we need to be aware of: any worsening pain, weakness, or neurological symptoms that could suggest a cord compression. We’re looking at renal function, hypercalcemia, worsening cytopenias. Again, this is where trending labs over time becomes very important. Looking at recurrent infections, rapidly progressing markers. These are all suggestive of relapsing disease. We’re really keeping a close eye on these patients. And remember, progression is not the same in every patient, so it might present differently depending on the patient’s biology and disease characteristics.

Advanced practice providers are often the consistent person in a patient’s treatment journey. And we help guide patients with their symptom management. We educate patients and their caregivers that this is a very complex disease. We’re really reinforcing disease characteristics. We’re helping our patients interpret the labs and the trends, early recognition of disease progression, toxicity management, and, I think really more importantly, coordination of care. We’re incorporating these newer complex therapies like CAR T-cell therapy and bispecifics, and we’re really shepherding our patients through these complex treatments.

I wish every oncology advanced practice provider knew that caring for patients with myeloma is about more than just following numbers or monoclonal protein spikes. You need to know the patient’s disease, how they presented, how their myeloma behaves, what they’ve previously received, what their individual risks are. Myeloma care is a long journey. It’s not 1 treatment. It’s many treatments over many years.

And I think advanced practitioners are often the clinicians who recognize these subtle changes. We’re with the patients throughout their treatment, managing their symptoms, and we can really tell when something’s not right. Knowing the patient as well as knowing the disease can make a big difference.