MRD-2 in the GHSG HD21 trial assessed by a validated circulating tumor DNA sequencing assay
Abstract
Abstract Beyond cure, major goals in patients with Hodgkin lymphoma (HL) are tailoring treatment to a patient’s individual risk for relapse to reduce acute and late toxicities, identifying candidates for early incorporation of novel agents, and making treatment affordable on a global level. Minimal residual disease (MRD) assessment by circulating tumor DNA (ctDNA) sequencing emerged as a promising strategy to achieve these goals; however, previous studies differed in sampling time points, assay validation, and definitions for MRD negativity. Here, we applied LymphoVista, a validated ctDNA sequencing assay for genotyping and MRD monitoring in lymphoma, to samples obtained from the German Hodgkin Study Group (GHSG) HD21 trial after 2 cycles of treatment (MRD-2) using a case-cohort design. Patients with positive MRD-2 result were at higher risk for relapse, progression, or death compared with MRD-2–negative patients (4-year progression-free survival [PFS], 36.7% vs 82.2%; hazard ratio, 5.3; 95% confidence interval, 2.0-13.8; P = .0008). After inverse probability weighting accounting for the number of events in the full reference set, patients with positive and negative MRD-2 results had 4-year PFS rates of 72.2% vs 95.3%. Combining MRD-2 with positron emission tomography after 2 cycles of BrECADD/eBEACOPP (PET-2) can identify patients at very low and patients at very high risk of relapse, progression, or death. In summary, these results suggest that MRD-2 assessment by LymphoVista allows for early outcome prognostication in patients with HL and could be used as a tool to improve treatment guidance on its own or in conjunction with PET-2.
Article Details
Authors (22)
Jan-Michel Heger
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Julia Mattlener
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Helen Kaul
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Justin Ferdinandus
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Jessica Schneider
Division of Biology and Biological Engineering, California Institute of Technology
Julia K. Schleifenbaum
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Gundolf Schneider
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Valdete Schaub
6Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany
Mathias Hänel
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Johannes C. Hellmuth
8Department of Medicine III, Ludwig Maximilian University Hospital Munich, Munich, Germany
Judith Dierlamm
9University Hospital Hamburg-Eppendorf, Hamburg, Germany
Sonja Martin
10Department of Hematology and Oncology, Robert Bosch Hospital, Stuttgart, Germany
Stephan Mathas
Julia Meissner
2Medicine V, University of Heidelberg, Heidelberg, Germany
D. Michiel Pegtel
15Cancer Center Amsterdam, Imaging and Biomarkers and Department of Pathology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Josée M. Zijlstra
Anna Ossowski
17West German Genome Center and Cologne Center for Genomics, Medical Faculty, University of Cologne, Cologne, Germany
Kerstin Becker
Michael Hallek
Department I of Internal Medicine, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, University Hospital of Cologne, Cologne, Germany
Bastian von Tresckow
1Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, and German Hodgkin Study Group, Cologne, Germany
Peter Borchmann
Uniklinik Koeln, Koeln, Germany
Sven Borchmann
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany