Multiple myeloma relapse means that the signs and symptoms of multiple myeloma return after treatment has led to an improvement of the condition.

Multiple myeloma is a type of blood cancer wherein cancerous plasma cells collect in the bone marrow. The cancerous cells push out healthy plasma cells, which work to fight infection, and create an antibody called M protein.

M protein is an abnormal antibody that causes damage in the body, such as tumors, bone and kidney damage, and weakened immune function.

Multiple myeloma is currently incurable and relapses by its nature. This means that periods of remission may follow periods of active disease in a cycle.

This article looks at the signs, symptoms, diagnosis, treatment, and overall outlook of multiple myeloma relapse.

a doctor is holding the hand of a person with relapsed multiple myelomaShare on Pinterest
Pekic/Getty Images

According to the International Myeloma Foundation (IMF), myeloma relapse is common. Most people will have several remissions and relapses throughout the course of their condition.

In people with no additional risk factors, the first period of remission may last for 2–3 years or longer.

One 2016 study looked at relapse rates in 511 participants with multiple myeloma following treatment in 2006–2014.

Within a 12-month period, 16% of the participants experienced early relapse. However, 84% had a relapse after 1 year or no relapse at the time of the follow-up.

The IMF defines a multiple myeloma relapse as a recurrence of the signs and symptoms of the condition after a time of improvement.

Initial symptoms of multiple myeloma can include:

People with multiple myeloma relapse may have more symptoms that are more severe, and impaired health may have a negative effect on their quality of life.

People may also experience the following symptoms with a multiple myeloma relapse:

People may also experience side effects from any medications they are taking, such as steroids.

Learn more about the signs and symptoms of multiple myeloma here.

Multiple myeloma currently has no cure and relapses by its nature. Symptoms may be worse during relapses than they were at the start of the diagnosis. This can make for a stressful experience for people with multiple myeloma.

One 2018 study focused on the impact that relapsed multiple myeloma can have on people’s quality of life. It found that people noticed conflicting information from doctors and that they needed more of a sense of continuity in their treatment.

Some other challenging consequences of multiple myeloma relapse that affected mental health included:

  • fatigue
  • partaking in risky behaviors
  • a feeling of vulnerability
  • self-care, in trying to manage symptoms themselves where people felt that doctors had not met their needs in treating pain

It can be challenging for doctors to implement a holistic care plan, given the individualistic nature of multiple myeloma. However, a person should be open with their doctor, making notes of symptoms before appointments and discussing honestly whether or not they feel the treatment is improving their symptoms and quality of life.

The study authors call for larger support teams to be available to people with multiple myeloma. In the meantime, a person could consider managing their mental health through resources available to them.

Learn about mental health resources and how to access them here.

To diagnose a relapse of multiple myeloma, doctors use a precise set of criteria from the International Myeloma Working Group.

To receive a diagnosis, people must meet one or more of the following:

  • a clear increase in the size of existing plasma cell tumors or bone lesions
  • calcium levels higher than 11 milligrams per deciliter (mg/dl)
  • a decrease in hemoglobin of 2 grams per dl (g/dl) or more, if not due to any therapy or unrelated health condition
  • an increase in serum creatinine, which is a muscle waste product present in the blood, of 2 mg/dl or more
  • a thickening of the blood due to serum protein
  • an increase of at least 0.5 g/dl in serum M protein
  • an increase of at least 200 mg per 24 hours in urine M protein
  • an increased difference between abnormal and normal free light chain levels of more than 10 mg/dl

Diagnostic tests

Doctors will carry out a range of tests to diagnose a multiple myeloma relapse. Such tests can include the following.

Test typeExample
blood testsblood count
chemistry panel
liver function test
myeloma protein measurements
serum-free light chain assays
serum β2 microglobulin
serum erythropoietin level
C-reactive protein
peripheral blood labeling index
urine testsroutine urine test
24-hour urine to measure total protein, electrophoresis, and immunoelectrophoresis
24-hour urine to test for creatinine clearance to check for elevated serum creatinine
bone testsskeletal survey with X-ray
MRI or CT scan
whole body PET scan
bone density test
bone marrow testsaspiration and biopsy of bone marrow
specific testing to check for any irregularities

Early relapse refers to the first cases of relapse a person may experience. As time goes on, multiple myeloma changes and becomes more complex, leaving more resistant clones to treat. This is known as subsequent relapse.

There are many treatment options available for both types of relapse.

Early relapse

Treatment for early relapse is individual to each person, so people will discuss a treatment plan with their healthcare team. Treatment for early relapse may include the following.

Autologous stem cell transplant

If a person has had an autologous stem cell transplant (ASCT) in their initial treatment and experienced remission lasting for 2–3 years or more, and if stem cells are available, they may be suitable for a second ASCT.

Learn more about ASCT for multiple myeloma here.

Repeating initial therapy

According to the IMF, if a person has not had a transplant but has had remission for 6–12 months, a doctor may repeat the therapy that successfully led to their remission.

In roughly 50% of people, repeating the initial therapy will lead to a second remission. This is especially the case for people whose first remissions lasted for 1 year or longer.

Learn more about multiple myeloma treatment options here.

Combination drug regimens

Doctors may use a combination drug regimen to treat a relapse. They may use drugs from the following categories:

  • immunomodulatory drugs
  • proteasome inhibitors
  • monoclonal antibodies

Doctors may use the following drugs from the above categories, which are suitable to use after one to three previous therapies:

Other, newer options that are suitable for follow-up treatment, but not front-line treatment, include:

Receiving fast-acting and effective treatment is important in managing early relapse. The following combinations are highly effective in treating early relapse:

  • daratumumab, lenalidomide, and dexamethasone
  • daratumumab, bortezomib, and dexamethasone

Subsequent relapse

Treatments for subsequent, or late, relapse are similar to early relapse treatments and may include the following drugs in a combination regimen:

  • bortezomib (Velcade)
  • lenalidomide (Revlimid)
  • cyclophosphamide (Cytoxan)
  • thalidomide (Thalomid)
  • carfilzomib (Kyprolis)
  • daratumumab (Darzalex)
  • elotuzumab (Empliciti)
  • ixazomib (Ninlaro)
  • pomalidomide (Pomalyst)

In people who have had one to three previous treatments, daratumumab in combination with lenalidomide and dexamethasone — or with bortezomib and dexamethasone — is a highly effective treatment.

Resistance

Over time, a person’s condition can become resistant to bortezomib, ixazomib, or lenalidomide. In this case, a person may try a combination of:

  • pomalidomide, cyclophosphamide, and dexamethasone
  • carfilzomib, pomalidomide, and dexamethasone
  • daratumumab, pomalidomide, and dexamethasone

Clinical trials

If the above treatments are not effective, a person may want to consider taking part in a clinical trial to try new drugs and treatments, which may be effective in treating resistant myeloma.

According to the IMF, some promising treatments currently in clinical trials include:

  • a new combination of daratumumab, carfilzomib, and dexamethasone
  • antibodies
  • new drugs, including isatuximab, selinexor, and venetoclax
  • a range of new CAR T cell therapy approaches

It is important to note that the industry is changing around clinical trials. For example, one type of CAR T cell therapy known as idecabtagene vicleucel (ide-cel) is the first therapy of this kind to receive Food and Drug Administration (FDA) approval for use in people with relapsed multiple myeloma.

The FDA is currently reviewing other CAR T cell therapies. This means that standard treatment options are changing and improving rapidly for people with this condition.

According to the American Cancer Society, the 5-year relative survival rate in 2010–2016 for people with multiple myeloma was 53%.

A 2016 study found that early relapse, or relapse within 12 months of starting therapy for multiple myeloma, leads to a higher risk of poorer outcomes.

However, these data are from 2016, and the survival rates for multiple myeloma are steadily improving due to advancing research and new and effective treatments.

Learn more about the outlook for multiple myeloma and what can affect it here.

Multiple myeloma relapse is a return of multiple myeloma symptoms after signs of improvement.

Treatment may include a combined regimen of medications. A person may also want to consider participating in clinical trials, as research is continuing to investigate new therapies.