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Publications

Journal Article Ahead of print

PubMed: 41979332 DOI: 10.1182/bloodadvances.2025019108

Interim assessment by circulating tumor DNA in primary mediastinal large B-cell lymphoma: a multicenter LYSA study.

Blood Adv

Authors: Vincent Camus, Daphné Krzisch, Alessio Bruscaggin, Emilie Lévêque, Mathieu Viennot, Luc-Matthieu Fornecker, Morgane Cheminant, Sebastien Bailly, Franck Morschhauser, Pierre Feugier, Sylvain Choquet, Eric Durot, Sylvain Carras, Caroline Delette, Ghandi Damaj, Agathe Waultier Rascalou, Pierre Lebreton, Katell Le Dû, Jean Galtier, Roch Houot, Nadine Morineau, Kamel Laribi, Laure Lebras, Lucie Obéric, Sandy Amorim, Simone Bocchetta, Pierre-Julien Viailly, Vinciane Rainville, Philippe Ruminy, Mélody Caillot, Lodovico Terzi di Bergamo, Deborah Piffaretti, Maria Cristina Pirosa, Matin Salehi, Gabriela Forestieri, Fanny Drieux, Elena-Liana Veresezan, Alexandra Traverse-Glehen, Marie Donzel, Lucie Burel, Elodie Bohers, Marie-Delphine Lanic, Dominique Penther, Stéphanie Becker, Pierre Decazes, David Tonnelet, Simon Draye-Carbonnier, Hervé Tilly, Fabrice Jardin, Davide Rossi … and 1 other author

Affiliations

  • Centre Henri Becquerel, Rouen, France.
  • APHP, Hopital Saint Louis, Paris, France.
  • Institute of Oncology Research, Bellinzona, Switzerland.
  • Institut de Cancérologie Strasbourg Europe, STRASBOURG, France.
  • Université Paris Cité, Necker-Enfants Malades University Hospital, AP-HP, Paris, France.
  • CHU Clermont-Ferrand, Clermont-Ferrand, France.
  • Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France.
  • Centre Hospitalier Universitaire Nancy and INSERM 1256, Nancy, France.
  • Groupe Hospitalier Pitié Salpétrière, APHP, Sorbonne Université, Paris, France.
  • Hôpital Robert Debré CHU de Reims, Reims cedex, France.
  • Univ. Grenoble-Alpes, University Hospital Grenoble-Alpes, Grenoble, France.
  • CHU Amiens, Amiens, France.
  • Caen University Hospital, Caen, France.
  • Centre Hospitalier Universitaire de Nîmes, Nîmes, France.
  • Groupe Hospitalier du Havre, Montivilliers, France.
  • Confluent Private Hospital, NANTES, France.
  • University of Bordeaux, Bordeaux, France.
  • CHU Rennes, Rennes, France.
  • HOSPITAL OF LA ROCHE SUR YON, La Roche Sur Yon, France.
  • Centre hospitalier le mans, Le Mans, France.
  • Centre d'hématologie et de cancérologie de la sauvegarde, lyon, France.
  • Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France.
  • Hopital Saint Vincent, Lille, Alabama, France.
  • INSERM U1245, Rouen, France.
  • INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Univ Rouen Normandie, Inserm U1245 and Centre Henri Becquerel, Rouen, France. Rouen, France.
  • Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
  • Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France.
  • Hospices Civils de Lyon, Pierre Bénite, France.
  • Inserm U1245, Centre Henri Becquerel, Rouen, France.
  • Centre Henri Becquerel, rouen, France.
  • CISEL, Le Coudray, France.

Abstract

Primary mediastinal large B-cell lymphoma (PMBL) achieves excellent outcomes with dose-dense immunochemotherapy, yet response assessment by PET remain limited. In this prospective multicenter observational study, we evaluated the clinical relevance of circulating tumor DNA (ctDNA) minimal residual disease (MRD) in newly diagnosed PMBL patients and assessed whether MRD enhances outcome discrimination beyond PET. Plasma and PET images were collected at baseline and after 2 and 4 cycles. ctDNA and tumor biopsy were analyzed by high-depth, error-corrected sequencing (limit of detection ~10⁻³). Associations between MRD, PET response and progression-free survival (PFS) were evaluated. Among 84 patients, baseline ctDNA was detected in 98%. After four cycles of treatment with R-CHOP14 or R-ACVBP, 87.7% had undetectable MRD. Persistence of MRD after four cycles of therapy was associated with shorter PFS (HR = 78.1 [95% CI: 9.5-641.8]). The 1-year PFS was 98.4% [95.4-100] for patients with undetectable MRD4 vs. 33.3% [13.2-84] for patients with detectable MRD4 (p<10⁻⁴). MRD4 showed a higher positive predictive value (89% vs. 50%) for disease progression than PET4, maintaining a similar negative predictive value (100% vs. 93%). In multivariate analysis, only PET4(-)/MRD4(-) remained associated with PFS (adjusted HR = 0.07 [95% CI: 0.01-0.90]). Plasma ctDNA represents a highly abundant source of genetic markers for tumor fingerprinting and disease monitoring. MRD detection following frontline therapy strongly complements PET response criteria in predicting outcome. These findings support the use of ctDNA monitoring as a valuable tool for future risk-adapted strategies in PMBL. NCT04980222.

MeSH

Cells, Circulating Tumor Dna, Lymphoma, B-Cell, Lymphoma, Neoplasms, Predictive Value Of Tests, Therapeutics, B-Lymphocytes, Hematologic Diseases