Multinational phase 2 trial of very early FDG-PET-guided targeted therapy for untreated advanced-stage classical Hodgkin lymphoma

Brentuximab vedotin combined with doxorubicin, vinblastine, and dacarbazine (A-AVD) improved outcomes in advance-stage classic Hodgkin lymphoma (cHL), but patients with a positive early interim PET have inferior prognosis. The multinational phase 2 EORTC-1537-COBRA trial evaluated very early ¹⁸F-FDG-PET-guided treatment adaptation after one cycle of A-AVD. The study, at 16 centers in seven countries, included 150 patients (54% males; median age 32 years; IQR 23-39) who received one cycle of A-AVD, after which 60% had a negative PET and 40% had a positive PET. PET-negative patients received five additonal A-AVD cycles, whereas PET-positive patients switched to six cycles of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dexamethasone, and dacarbazine). The median duration of follow-up for 145 evaluable patients was 30.1 months (IQR 24.6-36.4). The estimated median progression-free survival was 89.5% (80% CI 85.7-92.4). The most common grade 3-4 adverse events were neutropenia (35%), anemia (12%), and peripheral sensory neuropathy (6%). Serious adverse events occurred in 30%. No deaths occurred. The authors conclude that very early PET-guided therapy adaptation yielded high activity in advanced-stage cHL, while sparing most patients intensive chemotherapy.