What is minimal residual disease (MRD)?

After completing a course of treatment, there are few words that sound better to a patient than “complete remission.” It’s an indication that the treatment has worked, and there is no evidence of cancer based on scans or lab tests.

However, there is a different phrase that can be somewhat confusing to patients – minimal residual disease (MRD). This term is used often by physicians when treating patients with blood cancers, such as leukemia, lymphoma or multiple myeloma.

MRD refers to cancer cells remaining after treatment that can’t be detected by those same scans or tests. But what exactly does it mean for patients?

To learn more about minimal residual disease, we spoke with leukemia specialist Ghayas Issa, M.D., of MD Anderson’s Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) Moon Shot® team. Here’s what he shared.

How do you explain minimal residual disease to patients?

Minimal residual disease is a small number of cancer cells left in the body after treatment. These cells have the potential to come back and cause relapse in our patients.

In leukemia, for example, we look for response after chemotherapy treatment by looking under the microscope for cancer cells present in a bone marrow biopsy. When there are no cancer cells present, and the bone marrow is making normal cells, we call that a complete response.

However, we know that if we don’t do further treatment, a portion of these patients will experience a relapse. That means there were some leukemia cells hiding that we weren’t able to detect under the microscope. That is minimal residual disease, or perhaps a better term is measurable residual disease. Typically, these cells don’t cause any symptoms, but they have the potential to lead to a relapse.

If we can’t detect minimal residual disease under the microscope, how do we test for it?

We now have much more sensitive assays available to us that allow us to quantify MRD. These could include next generation genetic sequencing, where we can analyze bone marrow samples for genetic mutations. If there are mutations present, that means there is minimal residual disease, even though we can’t see anything under the microscope.

We can also use a technique called flow cytometry, which allows us look in the same samples for abnormal proteins on the surface of cells. By determining how many cells have abnormal proteins detected, we can get a better sense of residual cancer cells. Using these new assays, we routinely try to quantify whether a patient has MRD following standard treatment.

What are the implications for a patient who has evidence of minimal residual disease after treatment?

That’s difficult to say, because it’s not the same across all types of blood cancers. Some patients with MRD will have different responses than others. In general, if a patient has MRD, we need to do additional treatments to work toward the best outcome. If we do nothing, we know that the residual cells will cause a relapse.

It also depends on the timing of the MRD test. In my leukemia patients, if there is MRD after the first cycle of chemotherapy treatment, it tells me that I probably need to give more treatment — either a different medication or a different course of treatment. If there is still MRD after many rounds of chemotherapy, that is an indication that the patient may need to have a stem cell transplant, when otherwise it might not have been appropriate.

Ultimately, MRD is a marker that we need to be more aggressive in our treatment to try and prevent the cells from coming back.

What can cancer researchers learn from the residual cancer cells?

We can learn a great deal. These cancers can adapt to treatment, meaning the cancer we start with is not the same as what we have after treatment. By studying the minimal residual disease, we can learn more about what is left after treatment.

That helps us to do several things. First, it allows us to modify our treatment, either by adding medications that target specific vulnerabilities in the cancer cells, including medications that are especially good at killing even residual cells, or doing a stem cell transplant, which is able to take care of residual cells.

Currently, I work with a wonderful team through the MDS and AML Moon Shot to study these residual cancer cells in order to find new vulnerabilities. Through our research, we’re hoping to identify new treatments that we can use in the future to specifically eliminate minimal residual disease.

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