• Staging in myeloma is used to predict disease progression and survival, and it helps inform treatment options.
• Myeloma staging is based on the amount of myeloma cells a person has, how much damage they have caused in the body, and the genetic details of the cancer cells.
• Each case of myeloma is assigned a stage during initial diagnosis, and the stage may not change throughout the course of the disease.

When oncologists diagnose people with multiple myeloma, they assign a stage to the condition. Knowing the stage of myeloma allows doctors to better predict how the cancer is most likely to progress and determine which treatment options will be most effective.

Multiple myeloma stages can be confusing. Some doctors regard related precancerous conditions, such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), as early, asymptomatic stages of multiple myeloma. Some people with multiple myeloma have questions about whether their cancer will be assigned a new stage if it relapses, or whether staging is the main factor in deciding which treatment will be recommended.

“Staging is very different for myeloma,” wrote one MyMyelomaTeam member. “It’s not based on what needs to be done … it’s based on how much of your body is affected.” Another wrote, “Myeloma staging has such different rules — it is tough to learn everything.”

To address some of the confusion around this topic, MyMyelomaTeam invited Dr. Meera Mohan to discuss staging in myeloma. Dr. Mohan is a hematologist and oncologist with Froedtert & the Medical College of Wisconsin, where she also serves on the myeloma faculty.

What diagnostic procedures do oncologists use to determine the stage in a case of myeloma?

Typically, when we have a new patient, we order blood work to assess:

• Serum albumin levels
• Beta macroglobulin levels
• Serum light chain assay
• Serum protein electrophoresis
• Urine electrophoresis

The first two tests help us towards the staging, and the last three help us determine the specifications of the protein secreted by the myeloma cells.

A bone marrow examination is another standard procedure for newly diagnosed myeloma. After analyzing the bone marrow aspirate, we perform a cytogenetic study, which helps us get a snapshot of the biology of the cancer. And, if possible, we always try to incorporate imaging techniques, like a positron emission tomography (PET) computed tomography (CT) scan, and ideally magnetic resonance imaging (MRI) for newly diagnosed multiple myeloma patients.

Which stage are most people in when they begin to have symptoms that would lead to a myeloma diagnosis?

Stage 3 is rare as compared to stages 1 and 2 — the prevalence of stage 3 is significantly lower. So we see less stage 3, thankfully, compared to stage 1 and stage 2.

Does the stage of myeloma indicate the survival prognosis?

Yes, the stage does correlate with the survival prognosis — the higher the stage, the poorer the outcome. The five-year survival outcome in patients with R-ISS stage 1 myeloma is about 82 percent. Five-year survival in stage two is 62 percent, and five-year survival for stage 3 is 40 percent.

What are the earliest clues that someone might have myeloma? Some MyMyelomaTeam members say they had a bone fracture, while others had no symptoms at all.

Often, patients go for an annual physical examination, and they get routine blood work including a basic metabolic panel. A lot of patients get diagnosed in an asymptomatic setting, where the primary care physician notes an elevated level of protein in the blood.

Bone disease is very common in multiple myeloma patients. About 80 percent to 85 percent of patients tend to have bone disease. This can lead to a pathological fracture, which means the bones can fracture even without trauma.

They could have lesions in the bone, which we call lytic lesions. The myeloma cells tend to erode the bone and cause lytic lesions, which could be incidentally found on an X-ray. They could also have various symptoms like aches and pains, or maybe they are just not generally feeling well. But typically, symptoms such as weight loss or night sweats are much more prominent when you have a lot of tumor burden. They're not very common in the earlier stages of the disease.

Are treatment options based mainly on the stage of myeloma? Or are there other factors that play a role in which treatment options doctors recommend?

The standard approach for a newly diagnosed myeloma patient involves three stages. What we do first is induction chemotherapy. The goal of that initial stage of the disease treatment is to bring down the tumor burden.

The next stage is stem cell transplantation. The whole idea is that the transplantation is supposed to induce a deeper response. And then we have what we call maintenance therapy — the goal is to eradicate any tumor that is left in the body after they undergo a stem cell transplantation.

We know from the data available that patients with higher stage and higher risk disease do not have the same outcome as patients with lower stage or standard risk disease. So in the former, we try to treat patients with more effective treatment regimens, such as those including the newer monoclonal antibody daratumumab (Darzalex). Determining the stage at diagnosis is one way to stratify risk in the patients at diagnosis, but in reality, risk assessment is more dynamic throughout the disease course.

How long does maintenance therapy typically last?

We have emerging data that now supports maintenance till evidence of disease progression, also referred to as relapse. The goal of maintenance therapy is to make sure that the patient has no detectable myeloma cells in the body, which we assess via bone marrow aspiration analysis.

But in the typical scenario, duration of maintenance therapy should be balanced out with the side effects of the treatment and how well it’s tolerated. If patients are having trouble tolerating a treatment, they should have a discussion with their oncologist and see if there is any benefit to prolonging the maintenance therapy.

Is it possible to go into remission following effective treatment?

The majority of patients go into some level of remission after treatment. In advanced myeloma, the challenge is to maintain remission long term. Nevertheless, with the advances, we have a subset of patients who go into long-term remission, which is the ideal scenario.

If someone with myeloma goes into remission and then relapses, how is the relapsed myeloma staged?

The staging for myeloma is done at diagnosis. So, once the patient has a relapse, we run lab testing, we check kidney function and the level of calcium, and we assess further using PET-CT or magnetic resonance imaging. This gives us a better idea of the disease biology, and all the tests help us make decisions for future treatment.

But the stage is assigned at diagnosis. Then if a patient relapses, which the majority do, we consider any relapses to be a higher risk, but we don’t typically change the stage from what existed at the time of diagnosis.

What’s the most important thing for people with myeloma to know about the disease stages?

The highest stage leads to the poorest outcomes. So, when you have the highest stage disease, your oncologist might suggest alternative treatments or clinical trials, with the hopes of inducing remission.

Talk With Others Who Understand

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