Tracking ctDNA Levels Can Quickly Predict Response to Lymphoma Therapy

Laura Joszt

A blood test that tracks the rise and fall of circulating tumor DNA (ctDNA) levels can predict how patients with diffuse large B-cell lymphoma (DLBCL) will respond to therapy within days of starting treatment, according to a study led by researchers at Stanford University School of Medicine. The results were published in the Journal of Clinical Oncology, a publication from the American Society of Clinical Oncology.

About one-third of patients with DLBCL are not cured by conventional therapy, and it is important to be able to predict which patients will need additional or more aggressive therapy earlier.

“Although conventional therapy can cure the majority of patients with even advanced B-cell lymphomas, some don’t respond to initial treatment,” associate professor of medicine Ash Alizadeh, MD, PhD, said in a statement. “But we don’t know which ones until several months have passed. Now we can predict nonresponders within 21 days after the initiation of treatment by tracking the levels of ctDNA in a patient’s blood. We can look earlier and make a reliable prediction about outcome.”

Alizadeh and his colleagues studied ctDNA from 217 patients who were treated at 3 medical centers in the United States and 3 centers in Europe. The researchers compared levels of ctDNA before treatment with levels after the first and second rounds of conventional chemotherapy for each patient.
Read about how gender can predict response for certain treatments.
In 98% of the people studied, ctDNA was detectable before starting therapy. Once treatment started, the amount of ctDNA in the blood dropped for all patients, but the speed at which ctDNA levels dropped were important. Those with levels that dropped 100-fold after the first round or 300-fold by the second round were more likely to live 24 months or longer without recurrence compared with patients whose ctDNA levels dropped more slowly.

The researchers have previously shown that ctDNA levels can also predict recurrent in patients with lung cancer weeks or months before clinical symptoms arise.

“These findings confirm the value of tracking cancer genetics in the blood in real time,” Alizadeh said. “We are thinking about how to use the tools to best benefit patients and are very excited to test this approach in other types of cancers.”

Kurtz DM, Scherer F, Jin MC, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma [published online August 20, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.78.5246.
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