One of the most precise methods of detecting CLL cells in the body is completed using minimal residual disease (MRD) testing. 

What is MRD Testing?

MRD testing helps find the smallest number of cancer cells that may remain in a patient's body following treatment, or during remission periods. Its sensitivity is so high that it can identify remaining cancer cells that often go undetected by conventional clinical or laboratory tests. This detection ability helps give healthcare professionals highly accurate insight into the depth of a patient's response to treatment and offers predictions about the possibility of the cancer coming back.

How is MRD Testing Conducted?

MRD detection in CLL can be completed through a few methods. Flow cytometry, polymerase chain reaction (PCR), and next-generation DNA sequencing (NGS) are some of the most used techniques. These methods specifically target genes or immunophenotypic signatures specific to CLL cells. By identifying and counting these markers in the blood and bone marrow, MRD testing can determine the presence or absence of remaining cancer cells (residual disease). 

Typically, MRD test results are presented as a ratio or percentage, which shows the number of residual cells relative to a given number of standard cells. A lower MRD indicates better disease control and a decreased likelihood of relapse, whereas a higher MRD suggests a higher potential for disease recurrence. 

The Role of MRD in CLL Treatment

CLL patients often receive an MRD test after they have finished treatment with venetoclax (venclexta) + antibody therapy (obinutuzumab or rituximab). This treatment combination has successfully helped a significant number of CLL patients to become MRD negative—meaning the test finds no trace of CLL in their bloodstream (the test sample may also be bone marrow sponge or liquid collected via bone marrow tests). 

It's important, however, to differentiate MRD negativity from a definitive cure. Although the test might not detect any signs of the disease, small quantities below the test's detection threshold might still exist, posing a risk for potential relapse. Nonetheless, those who achieve MRD negativity often have an encouraging prognosis, frequently remaining in remission for extended periods.

Drs. Joshua Brody and Suchitra Sundaram elaborate on how MRD testing is used in CLL care. Watch their interview below: