Circulating Tumor DNA Is a Promising Biomarker for Progression in Diffuse Large B-Cell Lymphoma
In a study reported in The Lancet Oncology, Roschewski et al found that interim monitoring of circulating tumor DNA in patients with diffuse large B-cell lymphoma distinguished more and less rapid progression and that surveillance monitoring identified recurrence well before clinical evidence was apparent.
Study Details
The study involved use of next-generation DNA sequencing for retrospective analysis of cell-free circulating tumor DNA (VDJ gene rearrangement) in patients enrolled in one of three treatment protocols between May 1993 and June 2013. Patients had no evidence of indolent lymphoma and were previously untreated. Serial serum samples and concurrent computed tomography scans were obtained at specified times during most treatment cycles and for up to 5 years of follow-up.
Interim Monitoring
In total, tumor clonotypes were identified in pretreatment specimens from 126 patients who were followed for a median of 11 years. Interim monitoring of circulating tumor DNA at the end of two treatment cycles in 108 patients showed progression at 5 years in 41.7% of patients with detectable circulating tumor DNA vs 80.2% of those without detectable DNA (P < .0001). Detectable circulating tumor DNA had a positive predictive value of 62.5% and a negative predictive value of 79.8% for progression.
Surveillance
Surveillance monitoring was performed in 107 patients who achieved complete remission. A Cox proportional hazards model showed that the hazard ratio for clinical disease progression was 228 (P < .0001) for patients developing detectable circulating tumor DNA vs those who never had detectable DNA.
Detection of DNA was associated with a positive predictive value of 88.2% and a negative predictive value of 97.8% for progression. Patients developed detectable DNA at a median of 3.5 months before clinical evidence of disease was detected, including a median of 1.6 months earlier (range = 0.3–4.2 months) in five patients with early relapse and 7.4 months earlier (range = 0.0–200 months) in 10 patients with late relapse.
The investigators concluded: “Surveillance circulating tumour 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 tumour DNA is a promising biomarker to identify patients at high risk of treatment failure.”
Wyndham H. Wilson, MD, PhD, of the National Cancer Institute, is the corresponding author for the Lancet Oncology article.
The study was funded by the National Cancer Institute and Adaptive Biotechnologies. For full disclosures of the study authors, visit www.thelancet.com.
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