Multiple Myeloma 101: Causes, Types, and Stages

Not all cancers are created equally. Even though they might be similar in nature — i.e. uncontrolled division of abnormal cells in a part of the body — they’re not all treated the same way.

Myeloma is a cancer of the plasma cells that sees about 200,000 US cases a year, according to Dr. Rafael Fonseca of the Mayo Clinic.

Keep reading to learn about multiple myeloma, its treatment, and prognostic information from real experts.

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What is multiple myeloma?

Multiple myeloma belongs to the group of diseases we think about when we think about blood cancers. Specifically, myeloma is a form of adult bone marrow cancer that comes about when plasma cells convert into malignant cells.

Dr. Rafael Fonseca

Under normal circumstances, plasma cells help protect our bodies. They produce the antibodies that give us immunity. Occasionally, those cells become malignant, and that’s what we call myeloma. 

These malignant cells are usually restricted to the space inside the bones called the bone marrow. There are a number of problems that can come about because of the growth of malignant cells from myeloma. The cells grow, and they take up space.

A person may present with fatigue because they have anemia. The cells can also cause problems in the bones. They can erode the bone structures.

This can cause pain or in more extreme cases, even fractures. It also releases some of the calcium that our bones have into the bloodstream. Patients may have a high calcium content in their blood. 

Myeloma cells also produce a type of protein. Fragments of the protein can flow down into the urine. That can cause problems in the kidney in the form of renal failure.

What is multiple myeloma?

Multiple myeloma is a cancer of a cell called plasma cell. A plasma cell is part of your immune system. Normally your immune system is made to fight viruses and bacteria and one of its soldiers is called a plasma cell.

Particularly, plasma cells are supposed to produce antibodies, which we’ve heard a lot about recently. COVID antibodies, antibodies to zoster, all these things. 

These antibodies are proteins that help you fight and tag bad things so your immune system can know to kill those things.

In the case of multiple myeloma, one of these plasma cells goes haywire. It grows out of proportion to the other cells, and that’s really the definition of cancer.

When one cell gets selfish and replicates its own clone, it takes up the resources of the other cells. That’s what happens in multiple myeloma.

Dr. Nina Shah

One plasma cell grows and it starts taking up the space in the bone marrow. It starts producing a protein that eats the bone around it and that’s why people can have holes in their bones, or lytic lesions.

Then the protein that it produces—that antibody is now one antibody. It’s not a variety of antibodies. It’s just that one clone.

That’s why you will often hear the term monoclonal protein or monoclonal or clonal protein, M protein. That’s something that we can use to measure how many plasma cells there are.

It’s like the petals on the flower; the more petals you see around, the more you know they have flowers and that’s what we often use to measure in the blood.

The proteins that are produced from these cells can be in such high quantities that they also can have detrimental effects. That’s why some people with myeloma will say, “Well, my light chains were really up.”

That’s part of that M protein, those antibodies, and they can clog up the kidneys.

You hear about multiple myeloma as a disease that affects almost every part of the body—the bones, the kidneys, the blood system, and it all comes from having this one immune cell get a little out of whack. It’s supposed to help you, but in this case, it’s harming you.

Dr. Nina Shah

Types of Multiple Myeloma

Monoclonal Gammopathy of Undetermined Significance (MGUS)

It may be helpful to think of MGUS as tier 1. Generally speaking, patients with MGUS won’t have any outward symptoms and it’s actually not too rare. More than 2% of adults over 50 have it.

“That condition is when there’s very discrete growth of the plasma cells, usually that they’re going to be less than 10% of the cells in a person’s bone marrow,” Dr. Fonseca says.

Smoldering Multiple Myeloma

This condition can be considered tier 2. Smoldering multiple myeloma happens when the number of myeloma cells present is more than 10% but not enough for you to be symptomatic.

He says, “It will remain as such for as long as there is no evidence of complication.

Once we see that someone has complications, that’s when we say they have multiple myeloma, active myeloma, or simply, ‘myeloma.’”

Dr. James Berenson is also a myeloma specialist who runs his own private practice and has more than 35 years of experience. He reiterates this distinction concerning plasma cells.

“Plasma cells normally make lots of different kinds of antibodies and make up only about half a percent of your marrow. With myeloma, they make a lot larger of a percentage, and they’re all one type and make one antibody,” he says.

When this number increases, there’s a fine line between smoldering and active myeloma. Researchers are trying to find new ways of distinguishing between smoldering and active myeloma groups. Smoldering myeloma patients might start noticing symptoms like bone issues and fractures or kidney problems since the antibody can be toxic to the kidneys.

“We think there are some patients who have more advanced cases of smoldering multiple myeloma who should go ahead and start treatment,” Dr. Fonseca says.

Active Myeloma

Active myeloma, multiple myeloma, or myeloma is when a patient has enough myeloma cells that they start having symptoms. These can include worsening bone problems like fractures, a history of back pain, unexplained anemia, or advanced kidney problems like renal failure.

This is when a patient will most definitely need treatment.

Multiple myeloma diagnosis

For most patients that we diagnose, they’ll come because they’re having some symptoms. Some might come because they have a history of back pain. Sometimes they’re seen in the hospital because of kidney problems and it’s found out that those problems are due to the multiple myeloma.

Maybe a general practitioner finds that the person has anemia and it’s not otherwise explained. Then, the patient would go to a hematologist and would ultimately get diagnosed. 

There is a fraction of patients who are diagnosed with a premalignant condition called smoldering multiple myeloma where they may have abnormal cells and have detectable levels of the protein in their blood and urine but not show symptoms. The majority of those patients will not require treatment.

Dr. Rafael Fonseca

Multiple myeloma stages and prognosis

Dr. Fonseca urges patients to think about how far cancer research has come and how far it will go.

“When I first started in myeloma, we would tell patients they were looking at 2 or 3 years at best and we had almost no drugs. Now, the prognosis is measured in several or many years and sometimes even decades. 

“I remind patients of one thing all the time: if I see you today in 2019 and the life expectancy is 10 years, how will we treat myeloma in 2029? That is what we call the valley of options because with all the research being done, they will have options at that point that don’t exist today.”

Dr. Berenson agrees. He tells patients not to get caught up in the numbers the Internet might throw in their faces. Ask a real doctor about your treatment plan.

“Don’t get depressed by a lot of the prognostic news that’s going to make you feel like you’re going to die in five minutes. That’s not true anymore.”

Multiple myeloma treatment options

There are different types of treatments for multiple myeloma and there are always new clinical trials being conducted.

Chemotherapy for Myeloma

A common treatment for multiple myeloma might be the chemotherapy regimen RVd — Revlimid, Velcade, and dexamethasone. This is still the standard of care (along with autologous stem cell transplant) in new cases of multiple myeloma, according to Mayo Clinic.

RVd chemotherapy can cause neuropathy, GI issues like constipation or diarrhea, nausea, fatigue, and in more serious cases, blood clots. Dexamethasone is a steroid and many patients recall feeling anxious or being unable to sleep well.

Stem cell transplants for myeloma

In Favor of SCT

Dr. Nina Shah, myeloma specialist at the University of California, San Francisco (UCSF), says she considers stem cell transplant as part of the standard of care for newly-diagnosed multiple myeloma patients. She acknowledges not all doctors agree, but she favors doing transplants.

The three drugs at the upfront — Revlimid, Velcade, and Dexamethasone — are like the soap and sponge for cleaning a dirty pot. But Melphalan, which is the transplant drug, is the scouring pad. It really digs in and gets the deep myeloma cells that you couldn’t get. It’s another way of being smarter than the myeloma.

Dr. Shah describes the transplant process as having two parts, starting with a stem cell collection. “We can’t give you a very high dose of chemotherapy without damaging normal cells. Before we even give that dose of chemotherapy, we have first to collect blood stem cells so that your blood will recover from having that dose of chemotherapy.

“This is an outpatient procedure and can take about a few days. We put a big catheter, usually in your chest wall, or a big IV in your arm. Then we take out a bunch of blood and filter out those stem cells after having given you some medication to get those to your blood.

“Usually about a week between the injections and the procedure. Then after that, we do part two, which is the actual transplant. That’s when patients are, in our case, admitted to the hospital, although you can do it as an outpatient.”

Next comes one dose of chemotherapy, followed two days later by a replacement with the stem cells, which are thawed and given like a blood transfusion. Dr. Shah notes there are side effects that usually impact patients over the next two weeks or so:

• Nausea
• Vomiting
• Diarrhea
• Hair loss
• Infections

Patients will also require blood transfusions, as the blood system was “obliterated” and time is required for the stem cells to grow and repopulate.

Not Using SCT

Dr. Berenson says he no longer believes in stem cell transplants and bone marrow transplants for myeloma. He does not recommend them to his patients anymore.

“You’ve got to kill the myeloma, not the patient. Transplants involve a lot of non-specific chemo that does a lot of collateral damage. It doesn’t make people happy or give them a good quality of life. 

“Most doctors do still recommend them, but I certainly do not. I think we have better treatments that are better tolerated and offer a better quality of life. I don’t want people to have to go through holy hell with no upside,” Dr. Berenson says.

FAQs

What are the chances of it relapsing or being refractory?

Unfortunately, multiple myeloma is considered an incurable disease, but it is a disease that one person can live with for a very long time.

Dr. Nina Shah

We have patients who’ve lived 10, 15 years with it. It really depends on where that myeloma is going and what it’s like.

Sometimes we can predict that and sometimes we can’t, but on average, our standard myeloma patients are living longer than 10 years, at least, because we have new therapies.

What I tell all myeloma patients I meet is that, “You’ve been newly diagnosed and we’re starting therapy on you. We’re hoping that we can stretch out this time as long as possible so that we can have this first remission, meaning the first time you have a response that lasts as long as possible so that you don’t have to worry about it and you get back to your life and start being a person and not a patient.”

Is there a standard of care?

There are several guidelines that are published. One of the most common is called NCCN. From a patient perspective, that can be daunting and complex. I recommend starting with a patient organization like one of the ones I mentioned. 

We at Mayo have a set of guidelines we provide. It’s mostly directed towards providers, but it’s simple enough that they can be understood even if you’re not in medicine. They’re available online at msmart.org. That provides a general description of what we would prescribe for patients in different situations.

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