What Is MRD? Measurable Residual Disease Explained

MRD stands for minimal residual disease, a term used to describe the tiny number of cancer cells that remain in your body during or after treatment. These cells are too few to cause symptoms or show up on standard scans, but they can be detected by specialized lab tests sensitive enough to find one cancer cell among a million normal ones. MRD testing is most commonly used in blood cancers like leukemia and multiple myeloma, though it’s increasingly being explored for solid tumors as well.

Why MRD Matters

When cancer treatment appears to be working, imaging and basic bloodwork may show no sign of disease. But “no visible cancer” isn’t the same as “no cancer at all.” MRD testing goes deeper, measuring whether a small population of malignant cells is still lurking. Your MRD status after treatment is one of the strongest predictors of whether cancer will come back.

The numbers are striking. In multiple myeloma, patients who achieve MRD-negative status (meaning no detectable cancer cells remain) have roughly an 80 to 88 percent lower risk of disease progression and death compared to those who still test positive. Data from the GEM/PETHEMA trials showed that only 7 percent of MRD-negative myeloma patients experienced disease progression. In acute myeloid leukemia, MRD monitoring has become a critical tool for guiding treatment decisions, informing whether a patient needs more aggressive therapy or may be able to scale back.

How the Test Works

MRD testing uses laboratory techniques far more sensitive than standard blood tests. There are three main approaches, each with different strengths.

  • Flow cytometry works by tagging cells with fluorescent markers that stick to specific proteins on their surface. A machine then sorts through large numbers of cells, identifying the ones that look cancerous based on their protein signatures. This method can detect one cancer cell in 1,000 to one in 100,000, depending on the disease and the panel used.
  • PCR-based testing uses a technique that amplifies tiny fragments of DNA to search for genetic sequences unique to the cancer. Custom-designed primers target the specific mutation, and repeated amplification cycles make even trace amounts detectable. Sensitivity reaches up to one cancer cell in 100,000.
  • Next-generation sequencing (NGS) reads millions of DNA fragments simultaneously, scanning for cancer-specific genetic signatures. It’s the most sensitive option available, capable of detecting one malignant cell among a million normal ones. A 2025 consensus from the European LeukemiaNet now recommends NGS-based MRD testing for certain subtypes of acute myeloid leukemia after chemotherapy and before stem cell transplant.

What MRD-Negative and MRD-Positive Mean

An MRD-negative result means the test did not detect any remaining cancer cells at the sensitivity level used. An MRD-positive result means cancer cells were still found. The definition of “negative” depends on a predefined sensitivity threshold, and this threshold varies by disease. In acute myeloid leukemia, the cutoff is typically set at 10⁻⁴, meaning the test can detect one cancer cell in 10,000. In multiple myeloma, the bar is higher at 10⁻⁵, or one in 100,000.

Under optimal conditions, both NGS and advanced flow cytometry can push sensitivity even further, to between 10⁻⁵ and 10⁻⁶. That matters because the deeper the sensitivity, the more confident doctors can be that residual disease is truly absent. An MRD-negative result at 10⁻⁶ carries more weight than one at 10⁻⁴.

It’s worth noting that MRD-negative doesn’t guarantee a cure. A small number of patients who test negative still relapse. But as a group, MRD-negative patients consistently do far better than those who remain positive, which is why the result plays an increasingly central role in treatment planning.

What Happens During the Test

For blood cancers like myeloma and leukemia, MRD testing typically requires a bone marrow sample rather than a simple blood draw. A doctor collects a small amount of bone marrow, usually from the back of the hip bone, using a needle. The procedure takes about 15 to 30 minutes and is done under local anesthesia, though you’ll likely feel pressure and brief discomfort. The sample is sent to a lab at room temperature and needs to arrive within 48 hours of collection. Results generally come back in three to five days.

If you’re being treated for myeloma, your care team will need to know details like whether you’re on certain antibody therapies, because some drugs can interfere with how the test identifies cancer cells. Your disease status and any prior lab results help the lab interpret the findings accurately.

MRD Testing Beyond Blood Cancers

MRD was originally developed for leukemia and myeloma, but the concept is expanding into solid tumors like colorectal and lung cancer. Instead of analyzing bone marrow, these tests look for circulating tumor DNA (ctDNA), which are tiny fragments of cancer DNA that tumors shed into the bloodstream. A blood sample is all that’s needed.

The idea is the same: after surgery or treatment, ctDNA testing can reveal whether microscopic cancer remains before it becomes visible on a CT or PET scan. This could help doctors decide whether a patient needs additional chemotherapy or might safely skip it. However, ctDNA-based MRD testing for solid tumors hasn’t yet reached the same sensitivity as bone marrow testing for blood cancers. Early-stage tumors shed less DNA into the blood, making detection harder. Researchers are still working out the best positivity thresholds and figuring out how to use the results to guide treatment in everyday practice.

How MRD Results Shape Treatment Decisions

MRD results are increasingly used at specific decision points during treatment. In leukemia, doctors may check MRD status after an initial round of chemotherapy to see how well the cancer responded. If MRD remains positive, that may signal the need for a stem cell transplant or a change in therapy. If it’s negative, a less intensive approach might be appropriate.

In multiple myeloma, MRD testing can help determine how long to continue maintenance therapy. Some clinical trials now use MRD status as a primary endpoint, essentially measuring success by whether the test turns negative rather than waiting years to see if the cancer comes back. The MASTER trial, for example, used MRD-guided treatment decisions and reported a two-year progression-free survival rate of 87 percent overall, reaching 97 percent in patients without high-risk genetic features.

MRD monitoring also serves as an early warning system. Serial testing over time can catch a cancer that’s starting to regrow before it causes symptoms or shows up on imaging, potentially allowing earlier intervention.