Ask the Nurse: Minimal residual disease

September is Blood Cancer Awareness Month. As well as raising awareness of myeloma, we want to highlight that although incurable, myeloma is now more treatable than ever before. The future of myeloma detection and treatment is promising, with many new treatments and innovative monitoring techniques in development right now.

Minimal residual disease (MRD) testing is a highly sensitive method for detecting myeloma cells, which could transform approaches to treatment and monitoring.

In this month’s blog, we answer some of the questions we are asked on our Myeloma Infoline about measuring MRD.

What is minimal residual disease?

Someone may have as many as one million myeloma cells in their bone marrow sample when diagnosed with myeloma. Treatment for myeloma aims to kill as many myeloma cells as possible.

MRD, short for minimal residual disease, refers to the small number of cells that survive and remain in the bone marrow after successful treatment. MRD tests are remarkably sensitive, capable of detecting one myeloma cell among a million healthy cells. The number of surviving cells is so small they can’t be detected by routine tests or seen under a microscope.

Why might measuring MRD be useful?

Myeloma is a relapsing-remitting cancer. This means that after successful treatment, patients enter a period of remission or plateau where the myeloma is under control.

After reaching remission, many patients will remain well for some time – it may be months or years before the myeloma becomes active again. This happens because the residual myeloma cells (the minimal residual disease or MRD) eventually start to multiply until there are enough to be detected during check-ups, potentially leading to symptoms again.

Measuring MRD allows doctors to have a more detailed understanding of the number of myeloma cells that remain when a patient is in remission, even when the numbers are so small that standard tests can’t detect them.

Researchers and doctors are still investigating whether MRD can guide treatment options for myeloma patients. It is hoped that the test will help them to know how patients are responding to treatment and when they need to change or restart treatment after a break.

Do all myeloma patients have MRD measured?

In the UK, MRD testing is not widely available on the NHS for myeloma patients. Clinical trials aim to find out if and how MRD test results can best inform treatment decisions.

What does ‘MRD-negative’ mean?

If no remaining myeloma cells are detected in a patient’s sample, the result is ‘MRD-negative’. This indicates that there are no detectable cells at this level of sensitivity.

Trials have shown that MRD-negative patients are more likely to achieve a deeper, longer-lasting remission than those who have detectable residual myeloma cells.

What does an ‘MRD-positive’ mean?

If some myeloma cells are detected in a patient’s sample, their result is described as ‘MRD-positive’. This does not necessarily mean the myeloma has become active again.

Patients can be in remission and still be MRD-positive. However, clinical trials suggest that an MRD-positive result may mean a patient is more likely to relapse more quickly. This information could help healthcare teams determine how often to check for signs of relapse and decide on different treatment options to help patients stay well for longer.

When in remission, an MRD-positive status may indicate a low (and potentially stable) level of myeloma cells. It does not always mean the patient needs to restart or change their treatment. Healthcare teams will discuss this on an individual basis.

How is MRD tested?

There are different ways to measure MRD, and clinical trials are still exploring which is most effective for myeloma patients.

Many methods use a bone marrow sample for testing, which means the patient will need to have a procedure to extract fluid and cells from bone marrow, usually from the back of their pelvis (a bone marrow biopsy or trephine test). The procedure usually only takes a few minutes, and most people find the discomfort or pain manageable.

Does it have to be a bone marrow sample, or can my blood be used?

Some MRD tests use blood samples instead of bone marrow biopsies. These methods have yet to be widely used, even in clinical trials. These tests could reduce the need for patients to have uncomfortable biopsies in the future.

How might MRD testing be used in the future?

While MRD testing is not routine on the NHS for myeloma patients, ongoing research shows its potential to revolutionise myeloma detection.

Clinical trials show strong evidence that an MRD-negative result in a myeloma patient is a good indicator of longer-lasting remissions. However, research is ongoing to understand how to use MRD measurements to help make treatment decisions.

In the future, MRD testing may provide doctors with the information needed to offer individualised treatment plans, helping with decisions such as:  

• If the myeloma is in remission 
• The best time to take a break from treatment 
• When a change of treatment might be beneficial 
• When non-standard treatments to deepen remission might be useful 
• If relapse is likely, allowing healthcare teams to monitor and/or alter treatment as needed 

You can read more about the range of tests and investigations currently used for diagnosing and managing myeloma in our Tests and Investigations in myeloma Infoguide. 

If you have further questions or need support, contact us through the Myeloma Infoline at 0800 980 3332 (UK) or 1800 937 773 (Ireland) or use our Ask the Nurse email service.