Cost implications of reproductive outcomes in adult patients with advanced Hodgkin lymphoma in the European Union: evaluated from the Danish and Italian healthcare and societal perspectives

Aim: To estimate the reproductive and economic impact of interim positron emission tomography (iPET)-guided brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD) versus iPET escalated etoposide, doxorubicin, and cyclophosphamide, bleomycin, vincristine, procarbazine and prednisone (eBEACOPP) in patients of childbearing potential (POCBP) receiving frontline treatment for advanced Hodgkin lymphoma, using healthcare and societal perspectives in Denmark and Italy. Materials & methods: An exploratory cost-consequence analysis was developed using HD21 POCBP patient-level data, expert-defined composite measures of compromised reproductive ability, and cost data across Denmark and Italy. A hypothetical cohort of 1000 patients was modeled over 5- and 10-year horizons to project natural and assisted reproductive technology (ART) pregnancies and births based on treatment-specific gonadal function recovery and progression-free survival. Analyses incorporated pre-treatment fertility preservation, evolving fertility intentions and scenario analyses using a follicle-stimulating hormone (FSH)-only definition of reproductive recovery. Costs included counselling, preservation, ART, pregnancy outcomes and productivity loss. Results: Treatment with BrECADD was associated with lower fertility-related healthcare costs than eBEACOPP, reflecting higher rates of gonadal function recovery and increased natural conception, which reduced ART use. Savings over 5- and 10-year horizons were, respectively, €546,769 and €971,667 in Denmark, and €141,435 and €259,982 in Italy. Scenario analyses, including evolved intentions, FSH-only recovery and societal perspectives, showed consistent findings. Conclusion: BrECADD is associated with lower reproductive burden and reduced fertility-related costs compared with eBEACOPP, reflecting better preservation of gonadal function and reduced reliance on ART. These findings support the potential broader value of less gonadotoxic regimens in the FLHL setting.