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Gaucher Disease and Myeloma: What Patients and Families Should Know

Two thirds of Gaucher patients have some evidence of bone disease that is directly related to the disease. Gaucher bone disease may lead to serious orthopedic complications but it is not a cancerous condition. Doctors know that a much smaller number of people with GD can develop multiple myeloma, a malignancy of bone marrow plasma cells. Most patients with myeloma do not have Gaucher disease and most people with Gaucher disease do not develop myeloma. However, the risk of developing myeloma is higher in GD patients than in the general adult population in the US and Europe.

Dr. Neal Weinreb is a Gaucher disease specialist who is Voluntary Associate Professor of Human Genetics and Hematology at the University of Miami Miller School of Medicine and a member of the NGF Medical Advisory Board. He shares his perspective on the increased myeloma risk that comes with Gaucher disease and what patients and families need to know.

What Is Myeloma?

Myeloma is cancer that develops in the plasma cells, a type of white blood cells that helps your body fight infection by producing antibodies. Like all types of cancer, myeloma involves cells reproducing abnormally fast. As the myeloma cells proliferate, they crowd out the healthy red and white blood cells that your body needs to carry oxygen to your organs and fight disease.

Blood cells form in the bone marrow, spongy tissue inside your bones. As myeloma cells multiply, they can create substances that damage the bones, causing bone fractures (breaks) or pain. People with Gaucher disease are susceptible to bone damage, but the bone damage from Gaucher disease is not the same as that from myeloma.

Myeloma sometimes is called multiple myeloma because it often appears in more than one bone in the body.

Which Gaucher Disease Patients Are at High Risk for Myeloma?

Myeloma is more common among African Americans and generally affects people age 45 or older. In people with Gaucher disease, the risk factors are similar, although people with Gaucher disease who develop myeloma may develop it at a younger age.

Doctors know the risk of myeloma is higher in people with type 1 Gaucher disease than in the general population. Unlike some other conditions, such as Parkinson’s disease, carriers of Gaucher disease don’t appear to have a higher-than-average rate of developing myeloma. Researchers aren’t yet sure how myeloma risk affects people with type 3 Gaucher disease.

“Because of the nature of type 3, changing treatments will be introduced pretty rapidly. For instance, a new substrate-reduction drug is in trials, and most people with type 3 will eventually be switched to that medication,” Dr. Weinreb notes. Those changes “make it hard to find a stable population to follow over a long time. Depending on how rapidly gene therapy comes in, even in type 1 we may be seeing new a paradigm, and those treatments affect our ability to study it methodically.”

Why Does Gaucher Disease Raise Myeloma Risk?

According to Dr. Weinreb, the medical community generally agrees that Gaucher disease creates substances that seem to “turn on” the body’s immune system. “These substances can create a clone of plasma cells that react against specific lipids (complex fat molecules) in the body, against saposin protein, or both.”

According to the current theory, Gaucher patients may also be more prone to myeloma because:

  1. Gaucher disease continually provokes and stimulates the immune system.
  2. Under that stimulus, immune cells proliferate and keep growing.
  3. The rapidly growing cells are more likely to mutate and become cancerous.

“Gaucher disease does have a certain inflammatory component in general,” Dr. Weinreb adds. “Consequently, the immune system is hyperactive, which might set it up for developing a malignant change. Now researchers are trying to find out if there are specific substances involved in the process.”

What research says about myeloma and Gaucher disease

A Yale University study published in 2016 found that myeloma cells target specific lipids that are elevated in the blood. Gaucher disease affects enzymes that make it harder for the body to break down lipids. Many people with Gaucher disease have elevated lipids that might make them more vulnerable to myeloma cells.

“But the issue still requires further study,” notes Dr. Weinreb, who also is a member of the North American Scientific Advisory Board of the International Collaborative Gaucher Group (ICGG).

What Does ‘Higher Risk’ Mean to You?  

Doctors assign widely varying numbers to the myeloma risk associated with Gaucher disease. The latest data from the ICGG Registry shows a risk 10 times higher than the general population.

To develop myeloma, a person doesn’t have to have severe symptoms from Gaucher disease. Having any degree of Gaucher disease—even when it’s clinically mild—may be enough to raise your risk of developing myeloma.

But it’s important to remember that not every patient with Gaucher disease will eventually develop myeloma.

“The numbers sound frightening, but the overall number of patients is still a small minority,” says Dr. Weinreb. “In my own practice, over the last 20 to 30 years, I’ve treated 100 to 150 patients with Gaucher disease, and I’m aware of about 5 or 6 who’ve developed myeloma.”

“In a certain sense, the risk issue is a moving target,” says Dr. Weinreb. For unknown reasons, myeloma has become more frequent in the general population over the last 20 to 25 years. It may be that something in the environment irritates the immune system in certain people. Eventually, Gaucher specialists may be able to provide research that offers answers to the general population.

How MGUS relates to myeloma

Some people with Gaucher disease develop a more common myeloma precursor condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS is a buildup of plasma cells that aren’t cancerous. In some cases, MGUS advances into myeloma.

“People don’t develop myeloma without going through the stage of MGUS. But not everyone who develops MGUS gets myeloma,” says Dr. Weinreb.

About 3% of people over age 65 develop MGUS, Dr. Weinreb says, but only a minority of those patients go on to develop myeloma. “The risk is about 1% per year for patients with MGUS. The rate may be a little higher in Gaucher patients … [perhaps] about 3 to 4 times higher than in the general population.”

Myeloma Symptoms in People With Gaucher Disease

According to some research, as many as 62% of Gaucher disease patients worldwide have some kind of bone disease. With Gaucher disease treatment, most people feel better. Their anemia goes away, their platelet counts improve, they don’t have bone pain, and they feel invigorated.

But some people living with Gaucher disease in their 40s or 50s have new symptoms. They start to develop bone pain, have changes in their blood counts, or become newly anemic. The symptoms of myeloma are similar to symptoms of Gaucher-related bone disease: bone pain, anemia, and abnormal X-rays or MRIs. But myeloma, unlike Gaucher disease alone, can cause abnormal kidney function and high levels of calcium in the blood due to bone breakdown.

Dr. Weinreb believes any of those symptoms is a red flag to have some investigations done. “It doesn’t necessarily mean myeloma; it could be something else. But most people respond well to Gaucher disease treatment and live pretty normal lives on treatment, whether that’s enzyme therapy or substrate therapy. If there’s a change in status, that’s a signal that they need to be carefully evaluated for some other conditions, myeloma among them.”

Because of their higher risk for myeloma, U.S. doctors generally recommend testing for people with Gaucher disease, whether they receive Gaucher disease treatment or not. At age 40 or older, these individuals should have their serum immunoglobulin tested annually as part of routine Gaucher disease monitoring. Sometimes, doctors order urine tests to supplement blood tests.

Gaucher Disease Treatment’s Effects on Myeloma Risk

One unanswered question today: If a patient with Gaucher disease starts treatment early, will it prevent myeloma?

“We don’t know yet, because it still is older adults who have represented most cases of myeloma,” Dr. Weinreb explains. “In the next 10 to 20 years, we’ll be starting to have patients who are sufficiently old in the enzyme treatment era to tell us if the incidence of myeloma will go down because of treatment.”

At least one mouse model study has indicated that Gaucher disease treatment lowers the incidence of myeloma and a related cancer, lymphoma. There isn’t a similar human study yet.

Myeloma Treatment With and Without Gaucher Disease

Meanwhile, myeloma treatment is the same for people living with Gaucher disease as for those without it. And while there isn’t a cure for myeloma, treatments do exist.

Most myeloma treatment involves chemotherapy, sometimes with a stem cell transplant. The patient’s bone marrow cells are removed and saved while the patient undergoes intensive chemotherapy to kill the cancer. Then the bone marrow cells are re-implanted to rebuild a healthy immune system.

“Those treatments are based on the idea of wiping out myeloma cells in bone marrow,” says Dr. Weinreb. “But for someone with mild Gaucher disease who is not on treatment, we don’t yet know, if they develop myeloma, if they should also start Gaucher disease treatment.”

Meanwhile, myeloma treatment is changing very rapidly. As we were writing this blog, the FDA approved a new investigational treatment to help immune cells target myeloma cells. And in January, the FDA agreed to speed its review of a new drug for myeloma relapse after stem cell treatment.

“It’s a rapidly changing area,” Dr. Weinreb says. “And given the small number of Gaucher patients, we know even less.”

What to Do if You Have Gaucher Disease

The main thing to remember is that having higher risk for developing myeloma does not mean you will get it. The overall risk is still very low.

It’s important to:

  • See your Gaucher disease specialist if you notice anything unusual or experience new symptoms. You can use our treatment finder to search for providers by specialty, name, or location. You can also reach out and speak to a NGF Optimal Advisor.
  • Get all routine testing—especially after age 40. You should get tested even if you don’t need treatment for Gaucher disease. Learn more about optimizing your health.

Dr. Weinreb’s advice to all Gaucher disease patients: You should have regular exams by a doctor who’s knowledgeable about Gaucher disease.

Above all, he urges, “Don’t panic. Being ‘high risk’ does not mean you’ll develop myeloma.”


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