Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study

• Published in: The lancet oncology 2015-05, Vol.16 (5), p.541-549
• Main Authors: Roschewski, Mark, MD, Dunleavy, Kieron, MD, Pittaluga, Stefania, MD-PhD, Moorhead, Martin, PhD, Pepin, Francois, PhD, Kong, Katherine, MS, Shovlin, Margaret, RN, Jaffe, Elaine S, MD, Staudt, Louis M, MD-PhD, Lai, Catherine, MD, Steinberg, Seth M, PhD, Chen, Clara C, MD, Zheng, Jianbiao, PhD, Willis, Thomas D, PhD, Faham, Malek, MD-PhD, Wilson, Wyndham H, Dr
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor - genetics; Child; Data analysis; Data collection; Deoxyribonucleic acid; DNA; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Female; Heart attacks; Hematology, Oncology and Palliative Medicine; High-Throughput Nucleotide Sequencing; Humans; Laboratories; Lymphoma; Lymphoma, Large B-Cell, Diffuse - diagnostic imaging; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medical imaging; Middle Aged; Neoplastic Cells, Circulating; Patients; Review boards; Studies; Surveillance; Tomography, X-Ray Computed
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(15)70106-3

Summary Background Diffuse large-B-cell lymphoma is curable, but when treatment fails, outcome is poor. Although imaging can help to identify patients at risk of treatment failure, they are often imprecise, and radiation exposure is a potential health risk. We aimed to assess whether circulating tumour DNA encoding the clonal immunoglobulin gene sequence could be detected in the serum of patients with diffuse large-B-cell lymphoma and used to predict clinical disease recurrence after frontline treatment. Methods We used next-generation DNA sequencing to retrospectively analyse cell-free circulating tumour DNA in patients assigned to one of three treatment protocols between May 8, 1993, and June 6, 2013. Eligible patients had diffuse large-B-cell lymphoma, no evidence of indolent lymphoma, and were previously untreated. We obtained serial serum samples and concurrent CT scans at specified times during most treatment cycles and up to 5 years of follow-up. VDJ gene segments of the rearranged immunoglobulin receptor genes were amplified and sequenced from pretreatment specimens and serum circulating tumour DNA encoding the VDJ rearrangements was quantitated. Findings Tumour clonotypes were identified in pretreatment specimens from 126 patients who were followed up for a median of 11 years (IQR 6·8–14·2). Interim monitoring of circulating tumour DNA at the end of two treatment cycles in 108 patients showed a 5-year time to progression of 41·7% (95% CI 22·2–60·1) in patients with detectable circulating tumour DNA and 80·2% (69·6–87·3) in those without detectable circulating tumour DNA (p