Circulating Tumor DNA in Blood May Predict Recurrence in Patients With Diffuse Large B-Cell Lymphoma
A study assessing whether circulating tumor DNA encoding the clonal immunoglobulin gene sequence could be detected in the serum of patients with diffuse large B-cell lymphoma has found that surveillance circulating tumor DNA enabled detection of microscopic disease before it could be seen on CT scans. Interim circulating tumor DNA, according to the study, is a promising biomarker to identify patients at high risk of treatment failure. The study by Roschewski et al is published in The Lancet Oncology.
Study Methodology
Researchers used next-generation DNA sequencing to retrospectively analyze cell-free circulating tumor DNA in 126 patients with diffuse large B-cell lymphoma. All patients received the chemotherapy regimen EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) with or without rituximab (Rituxan) in clinical trials between 1993 and 2013. The patients had no evidence of indolent lymphoma and were previously untreated.
The investigators obtained serial serum samples from the patients before and during treatment, and the patients were followed up for a median of 11 years after the completion of therapy. The patients also had CT scans at the time of the blood testing as part of standard surveillance.
Study Findings
Interim monitoring of circulating tumor DNA at the end of two treatment cycles in 108 patients showed a 5-year time to disease progression of 41.7% (95% confidence interval [CI] = 22.2%–60.1%) in patients with detectable circulating tumor DNA and 80.2% (95% CI = 69.6%–87.3%) in those without detectable circulating tumor DNA (P < .0001). Detectable interim circulating tumor DNA had a positive predictive value of 62.5% (95% CI = 40.6%–81.2%) and a negative predictive value of 79.8% (95% CI = 69.6%–87.8%).
Surveillance monitoring of circulating tumor DNA was done in 107 patients who achieved complete remission. A Cox proportional hazards model showed that the hazard ratio for clinical disease progression was 228 (95% CI = 51–1022) for patients who developed detectable circulating tumor DNA during surveillance compared with patients with undetectable circulating tumor DNA (P < .0001). Surveillance circulating tumor DNA had a positive predictive value of 88.2% (95% CI = 63.6%–98.5%) and a negative predictive value of 97.8% (95% CI = 92.2%–99.7%) and identified the risk of disease recurrence at a median of 3.5 months (range = 0–200) before evidence of clinical disease.
“Surveillance circulating tumor DNA identifies patients at risk of recurrence before clinical evidence of disease in most patients and results in a reduced disease burden at relapse. Interim circulating tumor DNA is a promising biomarker to identify patients at high risk of treatment failure,” concluded the researchers.
Wyndham H. Wilson, MD, PhD, Head of the Lymphoma Therapeutics Section at the National Cancer Institute, is the corresponding author of The Lancet Oncology article.
Funding for this study was provided by the National Cancer Institute and Adaptive Biotechnologies. For full disclosures of the study authors, visit www.thelancet.com.
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