Patterns of presentation and outcomes in stage IV Hodgkin lymphoma: A report from the Children's Oncology Group (COG) AHOD1331 trial.

Outcomes for high-risk paediatric classic Hodgkin lymphoma (cHL) improved with the addition of brentuximab vedotin (Bv) to doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (AVEPC) chemotherapy. We evaluated the prognostic implications of distant extra-nodal sites contributing to stage IV disease. On AHOD1331 (NCT02166463), patients aged 2-21 years with high-risk cHL (stage IIB with bulk/IIIB/IVA/IVB) were randomized to 5 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC) versus Bv-AVEPC. Patients with stage IV disease, determined by protocol-defined and centrally reviewed Positron Emission Tomography - Computed Tomography (PET-CT), were identified. Baseline characteristics and progression-free survival (PFS) were compared by pattern of stage IV involvement (lung, bone, bone marrow, multiple sites and others). A total of 340 patients (median age 15 years) with stage IV disease were included. Of these patients, 173 (51%) received ABVE-PC and 167 (49%) Bv-AVEPC. PFS was highest with lung-only involvement (4-year PFS 88.6%) and lowest with bone marrow-only involvement (4-year PFS 71.9%). Compared to ABVE-PC, Bv-AVEPC improved PFS among all stage IV patients (hazard ratio [HR] 0.53, 90% confidence interval (CI) 0.33-0.85) and in the lung-only and bone-only subgroups. However, no PFS benefit was observed in those with bone marrow-only involvement. Among paediatric patients with stage IV cHL, Bv-AVEPC improved PFS across most patterns of stage IV disease, except in those with bone marrow involvement. These results will guide efforts to improve outcomes among children with stage IV cHL.