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MRD Assessment in CLL: FDA Clears clonoSEQ Assay

MRD Assessment in CLL: FDA Clears clonoSEQ Assay
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Published on September 8, 2020

Monitoring Disease Progression in CLL

The FDA has cleared the way for the clonoSEQ assay to be used to assess minimal residual disease (MRD) in the blood or bone marrow of patients with chronic lymphocytic leukemia (CLL).

The assay, which was developed by Adaptive Biotechnologies, is already used to detect and monitor MRD in multiple myeloma and acute lymphoblastic leukemia.

What is Minimal Residual Disease in CLL?

Minimal residual disease refers to the remaining number of cancer cells in a patient’s body during and after treatment. According to Adaptive Biotechnologies, the assessment is performed as a series of tests to evaluate prognosis, determine response to treatment, monitor disease during remission and predict potential relapse. Studies have shown that even the smallest amounts of residual disease can predict a patient’s long-term clinical outcomes.

“Looking with greater accuracy for persistent cancer cells can show how well treatment is working and may help inform important decisions such as changing or stopping therapy,” Dr. Brian Koffman, chief medical officer and executive vice president of the CLL Society, said in a press release. “In my own CLL journey, knowing my clonoSEQ MRD status has impacted the way my expert team of doctors and I manage my disease.”CLL Combination Therapies

CLL Clinical Trials Lead to Use of MRD Assay

The August 6 FDA clearance was based on two clinical trials. In an analysis of data from the CLL14 study (337 patients with CLL), those with undetectable MRD in their blood by clonoSEQ at three months post-treatment had a nearly seven-fold reduced risk of disease progression, compared with patients who did not reach undetectable MRD. At 30 months post-treatment, the probability of disease progression for CLL patients with undetectable MRD was only 5%, compared to 36% for patients with detectable disease.

In the other study, clonoSEQ MRD results were shown to be a significant predictor of disease progression and outcome in both blood and bone marrow samples.

According to the test’s website, clonoSEQ works by identifying the specific DNA sequence barcodes associated with a patient’s cancer and then tracking those sequences over time. A study of the test’s use in CLL found that the assay could detect a single cancer cell in 1 million healthy cells.

“We know that traditional CLL treatment response criteria are insufficient, so the ability to measure MRD with a test that is 100 times more sensitive than standard flow cytometry may change our approach to treating CLL,” Dr. John Pagel, principal investigator and chief of Hematologic Malignancies at the Swedish Cancer Institute, said in the release.

MRD Status in Cancer Patients

Over the years, there has been a debate about the importance of MRD-negativity. A survey of clinicians conducted by investigators from the University of Chicago Medical Center found that only 37% who use MRD testing in multiple myeloma make treatment decisions based on the results. (All the respondents said they were familiar with the concept.)

“There has been a general principle that the deeper the response, the longer it lasts,” said Dr. Jeff Sharman, a medical oncologist at Willamette Valley Cancer Institute and Research Center in Eugene, Oregon. He discussed MRD testing with Patient Power Co-Founder Esther Schorr at the 2018 American Society of Hematology (ASH) Annual Meeting in San Diego.

“Of course, we're not always right, but generally, the more cancer you get rid of, the longer you stay free from symptomatic cancer,” he told Schorr. “And MRD, the analogy I use, it's when my wife asks me to go to the refrigerator and find something, and I don't find it. It's not that it's not there. I just didn't look hard enough.”

MRD testing is not a “one-size-fits all” approach, added Dr. Nicole Lamanna, a hematologist/oncologist at Columbia University Herbert Irving Comprehensive Cancer Center in New York City.

“You can have somebody who may do very well on single-agent therapy for years and be fine and have no side effects, and so why muck with that because they're doing great?’” said Lamanna, who also spoke with Schorr at ASH 2018. “Versus other people who will need other therapy. And so, I think MRD is back, but we still have to learn how to use it and how to apply it.”

Learn more about clonoSEQ.

~Megan Trusdell

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Adaptive Biotechnologies Receives Expanded FDA Clearance for the clonoSEQ® Assay to Assess Minimal Residual Disease (MRD) in Patients with Chronic Lymphocytic Leukemia

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