Validation of the newly introduced Deauville Score 5a in patients treated for advanced-stage classic Hodgkin Lymphoma

The Lugano Imaging Committee recently refined the Deauville Score (DS), subdividing DS5 into DS5a (>2x liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography after two cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent GHSG randomized phase III trials. The primary analysis cohort was HD18 post-amendment standard arms (uniform treatment with six cycles of eBEACOPP); sensitivity cohorts were HD18 intention-to-treat, and HD21 eBEACOPP and BrECADD arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET2. DS5a was infrequent (4-6% across cohorts: 39/639; 67/1745; 33/568; 29/560). In the primary cohort, DS5 vs DS1-3 was associated with inferior PFS (hazard ratio [HR] 3.00, 95% confidence interval [CI] 1.25-7.23) and vs DS1-4 (HR 2.35, 95% CI 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1-4 (HR range 2.57-5.47), while DS4 according to the new definition did not consistently separate from DS1-3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. HD18 NCT00515554; HD21 NCT02661503.