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

作者：Vincent Camus, Daphné Krzisch, Alessio Bruscaggin, Émilie Lévêque, Mathieu Viennot, Luc‐Matthieu Fornecker, Morgane Cheminant, Sebastien Bailly, Franck Morschhauser, Pierre Feugier, Sylvain Choquet, Éric Durot, Sylvain Carras, Caroline Delette, Ghandi Damaj, Agathe Waultier Rascalou, Pierre Lebreton, Katell Le Dû, Jean Galtier, Roch Houot, Nadine Morineau, K 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, Élodie Bohers, Marie‐Delphine Lanic, Dominique Penther, Stéphanie Becker, Pierre Decazes, David Tonnelet, Simon Draye-Carbonnier, H Tilly, Fabrice Jardin, Davide Rossi, Pierre Sesques · 发表于：Blood Advances · 年份：2026 · DOI：10.1182/bloodadvances.2025019108 · 被引用次数：1 · 研究领域：Lymphoma Diagnosis and Treatment、Cancer Genomics and Diagnostics、CNS Lymphoma Diagnosis and Treatment

ABSTRACT: Primary mediastinal large B-cell lymphoma (PMBL) achieves excellent outcomes with dose-dense immunochemotherapy, yet response assessment by positron emission tomography (PET) remains limited. In this prospective multicenter observational study, we evaluated the clinical relevance of circulating tumor DNA (ctDNA) minimal residual disease (MRD) in patients with newly diagnosed PMBL 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 4 cycles of treatment with R-CHOP14 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, administered every 14 days) or R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone), 87.7% had undetectable MRD. Persistence of minimal residual disease after 4 cycles of therapy (MRD4) was associated with shorter PFS (hazard ratio [HR], 78.1; 95% confidence interval [CI], 9.5-641.8). The 1-year PFS was 98.4% (95% CI, 95.4%-100%) for patients with undetectable MRD4 vs 33.3% (95% CI, 13.2%-84.0%) for patients with detectable MRD4 (P < 10^-4). MRD4 showed a higher positive predictive value (89% vs 50%) for disease progression than PET4, (PET after 4 cycles of...