Design: Case-cohort biomarker validation within a randomised trial (EORTC-GELA H9)
Population: 257 patients with early-stage classic Hodgkin lymphoma; 105 progression events
Primary outcome: Progression-free survival
Effect: c-MET HR 0.75 (0.46–1.24); HLA class II HR 0.85 (0.50–1.45); CD68 HR 0.86 (0.52–1.44)

Investigators tested three of the most promising tissue biomarkers in classic Hodgkin lymphoma — c-MET, HLA class II and CD68 — on diagnostic biopsies from the EORTC-GELA H9 trial of early-stage disease. A case-cohort design included 257 patients with 105 progression events.

None predicted progression-free survival. Hazard ratios were 0.75 for c-MET (95% CI 0.46–1.24), 0.85 for HLA class II (0.50–1.45) and 0.86 for CD68 (0.52–1.44). Because none were significant alone, combinations were not tested.

Negative validation studies like this matter because promising biomarkers often enter pathology reports and treatment discussions before they are confirmed. The authors note that risk-adapted treatment in the trial, the exclusion of advanced disease and scoring difficulties may have masked an effect. Even so, the markers do not add enough to clinical risk factors to guide treatment in early-stage disease.

Do not use c-MET, HLA class II or CD68 staining to guide treatment in early-stage classic Hodgkin lymphoma.
Continue to rely on established clinical risk factors and interim PET response for treatment decisions.
The results may not apply to advanced-stage disease, which was excluded.
Interpret single-centre biomarker associations cautiously until validated in trial cohorts.

Why it matters

It removes three candidate markers from the list of tests that might have changed early-stage treatment.

The statistics, in plain English

Each hazard ratio's confidence interval crosses 1.0, so none of the markers was linked to a clear change in progression risk. A case-cohort design samples all patients who had events plus a random subset of the rest, which is efficient but needs special weighting, as used here.