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

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.

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Journal
Blood Advances
Published
2026-04-14
DOI
https://doi.org/10.1182/bloodadvances.2025019108
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
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0.00

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article

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

Alessio Bruscaggin, Émilie Lévêque, Lucie Obéric, Lodovico Terzi di Bergamo et al.
Blood Advances
Lymphoma Diagnosis and Treatment
article

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

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

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.

Blood Advances
Hôpital Necker-Enfants Malades (FR), Université de Bordeaux (FR), Inserm (FR), Université Paris Cité (FR), Centre Hospitalier Universitaire de Grenoble (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Toulouse (FR), Sorbonne Université (FR), Institut Necker Enfants Malades (FR), Institut de Cancérologie Strasbourg (FR), Ente Ospedaliero Cantonale (CH), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Institute of Oncology Research (CH), Centre Hospitalier Universitaire de Nîmes (FR), Centre Hospitalier Universitaire de Reims (FR), Roche (France) (FR), Hôpital Lyon Sud (FR), Pitié-Salpêtrière Hospital (FR), Groupe Hospitalier du Havre (FR), Centre de Recherche en Cancérologie de Lyon (FR), Centre Hospitalier du Mans (FR), Hôpital Robert-Debré (FR), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Hôpital privé du Confluent (FR), Hôpital Saint-Louis (FR), Centre Hospitalier Départemental Vendée (FR), Centre Virchow-Villermé (FR), International YMCA University of Applied Sciences (DE), Centre Hospitalier Universitaire de Rennes (FR), Centre Henri Becquerel (FR), Groupe de Recherche sur les formes Injectables et les Technologies Associées, Génomique du cancer et du cerveau, Université de Rouen Normandie (FR), Université Grenoble Alpes (FR), Université de Reims Champagne-Ardenne (FR), Université de Caen Normandie (FR)
Ligue Contre le Cancer, Groupement des Entreprises Françaises dans la lutte contre le Cancer
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Openalex Percentile: Top 22%
Lymphoma Diagnosis and Treatment
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