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PubMed2026

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2× liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, 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. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans↗

PubMed2026

MRD-2 in the GHSG HD21 trial assessed by a validated circulating tumor DNA sequencing assay.

Beyond cure, major goals in patients with Hodgkin lymphoma (HL) are tailoring treatment to a patient's individual risk for relapse to reduce acute and late toxicities, identifying candidates for early incorporation of novel agents, and making treatment affordable on a global level. Minimal residual disease (MRD) assessment by circulating tumor DNA (ctDNA) sequencing emerged as a promising strategy to achieve these goals; however, previous studies differed in sampling time points, assay validation, and definitions for MRD negativity. Here, we applied LymphoVista, a validated ctDNA sequencing assay for genotyping and MRD monitoring in lymphoma, to samples obtained from the German Hodgkin Study Group (GHSG) HD21 trial after 2 cycles of treatment (MRD-2) using a case-cohort design. Patients with positive MRD-2 result were at higher risk for relapse, progression, or death compared with MRD-2-negative patients (4-year progression-free survival [PFS], 36.7% vs 82.2%; hazard ratio, 5.3; 95% confidence interval, 2.0-13.8; P = .0008). After inverse probability weighting accounting for the number of events in the full reference set, patients with positive and negative MRD-2 results had 4-year PFS rates of 72.2% vs 95.3%. Combining MRD-2 with positron emission tomography after 2 cycles of BrECADD/eBEACOPP (PET-2) can identify patients at very low and patients at very high risk of relapse, progression, or death. In summary, these results suggest that MRD-2 assessment by LymphoVista allows for early outcome prognostication in patients with HL and could be used as a tool to improve treatment guidance on its own or in conjunction with PET-2.

Humans↗