Minimal Residual Disease: Application in Blood Cancers

A diagnosis of chronic lymphocytic leukemia (CLL) can mean a long road with many twists and turns as patients try to achieve long-term remission from this chronic, complex and progressive form of blood cancer.

Living with CLL has meant co-existing with a disease often marked by a cycle of remissions and relapses, and becoming more challenging to treat with each relapse.[i] Until recently, physicians had only a limited treatment arsenal and imprecise tests to measure evidence of disease, and the idea of measuring cancer cells to the point that they become “undetectable” was a far-fetched dream.[ii] 

But as blood cancer treatment approaches evolved, the treatment paradigm expanded from chemo-immunotherapy based regimens to an array of targeted and chemo-free options.[iii]

“In parallel with these important therapeutic advances, we also are getting closer to finding protocols that may one day help doctors to tell patients they can stop treatment and have a chance to live longer without their disease progressing,” says John Hayslip, medical director, AbbVie. “A decade ago, it was hard to imagine this as a possibility.”

New Measurement Tools

Understanding the number of residual leukemic cells remaining in the blood after treatment is becoming an important new measure in hematology, in addition to the widely-accepted outcomes of progression-free survival (PFS) and overall survival (OS).

Minimal residual disease (MRD)-negativity, also known as undetectable MRD (uMRD), is an objective measure of response to treatment, defined by a certain number of leukemia cells found among white blood cells in the blood or bone marrow. With increasingly sophisticated diagnostics like polymerase chain reaction (PCR) or flow cytometry, these tests can measure cells with a sensitivity of less than one CLL cell in 10,000 normal cells, and some diagnostics are even more sensitive.

MRD may also be associated with the depth of response, enabling physicians to make more informed treatment decisions.[iv]

“It’s a measure beyond what we had in the past,” Hayslip explains. “Before we could test for MRD, a patient could go into what we call complete remission, where you couldn’t detect any more signs of cancer in the peripheral blood. But we knew there were probably still cancer cells running around in the patient’s body, and we just had no way of detecting them.”

“I believe that the eradication of residual cancer cells (“MRD-negativity”) is an achievable goal for more patients than ever before with all types of blood cancers, including CLL, who live each day hoping their cancer will remain in remission,” says Neil Gallagher, M.D., vice president and head, global oncology development, AbbVie.

“The first time I was told I achieved undetectable MRD, that changed everything,” said Deborah Sims, mother of three children who was diagnosed with CLL at a young age of 38. “I wasn’t expecting to get there.”

Going Further

MRD, as a biomarker, may reflect a patient’s response to treatment or function as a prognostic tool to assess risk of future relapse.[v],[vi] Regulatory bodies such as the U.S. Food and Drug Administration (FDA) recently released a draft guidance for inclusion of MRD as an endpoint in clinical trials to standardize the measurement across the industry.

“As we continue to make advancements in how we measure residual disease, it’s exciting to see the application in hematologic oncology,” Dr. Gallagher says.

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