Circulating tumor DNA analyses of molecular tumor burden are superior to PET-assessed responses in patients with advanced stage classic Hodgkin lymphoma treated on SWOG S1826

作者：Julia Paczkowska, Marcin Kaszkowiak, Michael LeBlanc, Chip Stewart, Alex F. Herrera, Juan Carlos Fernandez del Castillo, Sharon M. Castellino, Sarah C. Rutherford, Andrew M. Evens, Kelly Davison, Hongli Li, Donna Neuberg, Mark A. Murakami, Jasmine Makker, Brad S. Kahl, John P. Leonard, Nancy L. Bartlett, Sonali M. Smith, Joo Y. Song, Kara M. Kelly, Gad Getz, Jonathan W. Friedberg, Margaret A. Shipp · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-351 · 被引用次数：7 · 研究领域：Lymphoma Diagnosis and Treatment、Cancer Genomics and Diagnostics、Cancer Immunotherapy and Biomarkers

Abstract Introduction: Classic Hodgkin lymphomas (cHL) have genetic bases for enhanced PD-1 signaling and the highest reported response rates to PD-1 blockade. In the S1826 phase III trial, patients (pts) with newly diagnosed advanced stage cHL who were treated with nivolumab (N)-AVD, vs brentuximab-vedotin (BV)-AVD, had improved progression-free survivals (PFS), establishing a new standard of care. We used our recently developed ctDNA assay to evaluate changes in molecular tumor burden (MTB) and compared ctDNA- and PET-assessed responses in S1826. Methods: The first 388 trial pts with baseline, cycle 3 day 1 (C3D1) and end-of-therapy (EOT) plasma samples (and germline DNAs) were analyzed with the targeted sequencing assay that captured recurrent single nucleotide variants, indels, somatic copy number alterations (SCNAs), structural variants, sites of physiologic and aberrant somatic hypermutation and EBV status. Low-pass whole genome sequencing provided an orthogonal assessment of SCNAs. A newly developed algorithm, MTB-Tracker, identified clustered variants and measured treatment (Tx)-related changes in MTB (log-fold changes in hGE/ml) that were compared to centrally reviewed PET scans (Deauville scores 1-3 [-] vs 4-5 [+]) at C3D1 (interim [i] PET) and EOT. Results: 375/388 (97%) pts with detectable clustered variants at baseline were included in the analysis. Clinical characteristics of these pts – median age 25y (range, 12-83y), 28% <18y, 10% >60y, 37% with ...