Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing

David M. Kurtz, Michael R. Green, Scott V. Bratman, Florian Scherer, Chih Long Liu, Christian A. Kunder, Kazuhiro Takahashi, Cynthia Glover, Colm Keane, Shingo Kihira, Brendan Visser, Jason Callahan, Katherine A. Kong, Malek Faham, Karen S. Corbelli, David Miklos, Ranjana H. Advani, Ronald Levy, Rodney J. Hicks, Mark HertzbergRobert S. Ohgami, Maher K. Gandhi, Maximilian Diehn, Ash A. Alizadeh

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Recent studies have shown limited utility of routine surveillance imaging for diffuse large B-cell lymphoma (DLBCL) patients achieving remission. Detection of molecular disease by immunoglobulin high-throughput sequencing (Ig-HTS) from peripheral blood provides an alternate strategy for surveillance. We prospectively evaluated the utility of Ig-HTS within 311 blood and 105 tumor samples from 75 patients with DLBCL, comparing Ig-HTS from the cellular (circulating leukocytes) and acellular (plasma cell-free DNA) compartments of peripheral blood to clinical outcomes and 18fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT; n = 173). Clonotypic immunoglobulin rearrangements were detected in 83% of patients with adequate tumor samples to enable subsequent monitoring in peripheral blood. Molecular disease measured from plasma, compared with circulating leukocytes, was more abundant and better correlated with radiographic disease burden. Before treatment, molecular disease was detected in the plasma of 82% of patients compared with 71% in circulating cells (P = .68). However, molecular disease was detected significantly more frequently in the plasma at time of relapse (100% vs 30%; P = .001). Detection of molecular disease in the plasma often preceded PET/CT detection of relapse in patients initially achieving remission. During surveillance time points before relapse, plasma Ig-HTS demonstrated improved specificity (100% vs 56%, P < .0001) and similar sensitivity (31% vs 55%, P = .4) compared with PET/CT. Given its high specificity, Ig-HTS from plasma has potential clinical utility for surveillance after complete remission.

Original languageEnglish (US)
Pages (from-to)3679-3687
Number of pages9
JournalBlood
Volume125
Issue number24
DOIs
StatePublished - Jun 11 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kurtz, D. M., Green, M. R., Bratman, S. V., Scherer, F., Liu, C. L., Kunder, C. A., Takahashi, K., Glover, C., Keane, C., Kihira, S., Visser, B., Callahan, J., Kong, K. A., Faham, M., Corbelli, K. S., Miklos, D., Advani, R. H., Levy, R., Hicks, R. J., ... Alizadeh, A. A. (2015). Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood, 125(24), 3679-3687. https://doi.org/10.1182/blood-2015-03-635169