Even when multiple myeloma treatment works well, a very small number of cancer cells can sometimes remain in the body. These leftover cells are called minimal residual disease (MRD), also known as measurable residual disease.

MRD testing gives myeloma specialists a closer look at how well treatment is working. It can help show whether your blood cancer is responding to myeloma therapy, whether remission may last longer, and whether there’s a higher chance of relapse later on.

In this article, we’ll explain how MRD testing works, what MRD results mean, and how doctors may use MRD results to guide multiple myeloma treatment recommendations.

What Is Minimal Residual Disease in Multiple Myeloma?

Minimal residual disease refers to the tiny number of myeloma cells that may remain after treatment. These cells are so small in number that other tests may not find them.

Someone who is MRD-positive still has detectable myeloma cells after treatment. Someone who is MRD-negative has no detectable myeloma cells using very sensitive testing methods.

However, MRD-negative status doesn’t necessarily mean the cancer is cured. It means the tests couldn’t find any remaining cells at the level they were able to measure.

Doctors may check MRD at different times during your myeloma treatment journey. Your MRD status can change over time.

In the past, doctors mainly looked at whether a person achieved a complete response (complete remission). This meant there were no obvious signs of active myeloma after treatment. However, many of these individuals later relapsed despite having previously responded to treatment.

Today, many myeloma experts believe MRD testing gives more detailed information than complete response alone. Research has shown that people who become MRD-negative often have longer remissions and better outcomes than people who remain MRD-positive.

Doctors may also use imaging tests, blood tests, and the CRAB criteria (high calcium, renal (kidney) problems, anemia, and bone damage) alongside MRD testing to monitor multiple myeloma and guide treatment decisions.

How Is MRD Tested?

MRD testing usually involves testing a bone marrow sample. Sometimes a blood sample and/or imaging scans may also be included.

Different tests can detect very tiny amounts of myeloma cells that older methods may miss.

Bone Marrow Sampling

Most MRD tests are done using a bone marrow biopsy or bone marrow aspirate. During these procedures, healthcare providers remove a small sample of bone marrow (usually from the hip bone).

The sample is then studied in a laboratory using highly sensitive testing methods.

Because myeloma starts in plasma cells inside the bone marrow, bone marrow testing remains one of the most accurate ways to check for residual disease.

Flow Cytometry

Flow cytometry identifies proteins found on the surface of cells collected in samples.

Healthy plasma cells and myeloma cells have different protein patterns. Flow cytometry helps specialists count how many abnormal plasma cells are still present after treatment.

Researchers and doctors are still learning exactly how to use MRD findings to make recommendations about treatments.

Some centers now use next-generation flow cytometry, which is even more sensitive and can detect one myeloma cell among hundreds of thousands or even millions of healthy cells.

Next-Generation Sequencing

Next-generation sequencing (NGS) looks for unique genetic changes in myeloma cells in samples.

This method can detect extremely small amounts of leftover disease. The U.S. Food and Drug Administration (FDA) has approved an NGS-based test called clonoSEQ for MRD testing in multiple myeloma.

Blood-Based MRD Testing

Researchers are also studying blood-based MRD testing, including mass spectrometry tests.

Blood tests may eventually make MRD monitoring easier and less invasive than repeated bone marrow biopsies. However, many myeloma experts still consider bone marrow samples the standard approach for MRD assessment in myeloma today.

Imaging Tests

Some people with multiple myeloma may have disease outside the bone marrow.

Because of this, doctors sometimes combine MRD testing of bone marrow with imaging tests, such as positron emission tomography (PET) and computed tomography (CT) scans. Imaging can help detect myeloma in areas that a bone marrow biopsy might miss.

When Is MRD Tested?

“How often do they do the MRD testing for you?” asked a MyMyelomaTeam member. There’s no single schedule recommended for everyone.

Doctors may check MRD at several different times, including:

• After initial treatment
• After a bone marrow transplant
• During maintenance therapy
• When relapse is suspected
• During follow-up monitoring

MRD Status Can Change

It’s important to note that someone who was previously MRD-negative can later become MRD-positive. “Just went from MRD-neg to MRD-pos,” said one MyMyelomaTeam member. “Nevertheless, I’m still staying hopeful.”

Many myeloma specialists agree that repeated MRD testing over time may provide more useful information than a single test result alone.

How Do MRD Results Guide Multiple Myeloma Treatment?

MRD results can help doctors better understand how your myeloma is responding and when it might be time to try a new treatment.

One MyMyelomaTeam member shared how his minimal residual disease negativity guided his treatment plan: “After a second MRD-negative test and clear whole body scan, we decided to stop teclistamab and continue immunoglobulin and monthly monitoring.”

Researchers and doctors are still learning exactly how to use MRD findings to make treatment decisions. Still, MRD testing is becoming increasingly important in real-world multiple myeloma care and clinical trials.

MRD-Negative Status May Suggest Better Outcomes

Studies consistently show that people who become MRD-negative tend to have:

• Longer remission periods
• Lower risk of relapse
• Better progression-free survival
• Better overall survival

This is true across many different myeloma treatments and risk groups.

Someone who is MRD-positive still has detectable myeloma cells after treatment. Someone who is MRD-negative has no detectable myeloma cells using very sensitive testing methods.

However, MRD-negative status doesn’t guarantee that myeloma will never return. Some myeloma cells may still remain at levels below what current tests can detect.

MRD-Positive Results May Help Identify Higher-Risk Disease

If MRD testing still finds myeloma cells after treatment, it may suggest:

• The treatment didn’t fully eliminate the cancer
• The disease may be more resistant to therapy
• There could be a higher risk of relapse

This information may help specialists decide whether closer monitoring or additional treatment could be helpful.

For example, doctors may consider changing therapy, continuing maintenance treatment longer, or recommending clinical trials in some situations.

MRD Testing May Help Personalize Treatment in the Future

Right now, there are still unanswered questions about how best to use MRD results.

For example, researchers are studying:

• How MRD-positive disease should alter treatment plans
• How often MRD testing should be repeated
• Which MRD testing methods are most accurate
• Whether some people can safely stop treatment after sustained MRD negativity

Most myeloma experts agree that MRD testing is promising, but treatment decisions should still consider the whole picture. Factors include symptoms, imaging, blood work, details about cancer cell mutations, and overall health.

Talk With Your Myeloma Specialist About MRD Testing

MRD testing can provide important information about how your treatment is working and how your myeloma may behave over time.

Not everyone with multiple myeloma will need minimal residual disease testing, and recommendations may differ depending on your treatment plan, stage of disease, and access to specialized testing.

Here are some questions to ask your myeloma specialist:

• Does MRD testing make sense for me?
• What do my results mean?
• How does MRD status affect my treatment plan?
• Is repeat testing recommended?

It’s also important to keep up with all recommended follow-up visits, blood tests, imaging scans, and bone marrow testing when needed.

The more information your oncology team has, the better they can personalize your treatment journey.

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