Renfro, Lindsay A.

ABSTRACT Purpose Despite 5‐year survival rates of over 90% among children and adolescents/young adults (CAYAs) with classic Hodgkin lymphoma (cHL), 15%–20% relapse after frontline therapy. Prior analysis of frontline Children's Oncology Group (COG) clinical trials demonstrated that, despite similar rates of relapse, non‐Hispanic Black (NHB) and Hispanic (vs. non‐Hispanic White [NHW]) patients experienced higher post‐relapse mortality. It is unknown whether post‐relapse disparities persist when second‐line treatment is delivered in a cooperative group trial setting. We examined overall survival (OS) by race and ethnicity in CAYAs enrolled in COG trials for relapsed/refractory (r/r) cHL. Methods A pooled analysis of individual‐level data from CAYAs (≤ 29 years) receiving therapy for r/r cHL on COG clinical trials (2001–2016) was conducted. The Kaplan–Meier method estimated 3‐year OS by racial and ethnic groups. Cox regression models examined associations of race and ethnicity and OS, adjusted for age, insurance, first versus ≥2 relapse, and time from initial diagnosis to relapse trial enrollment. Results Among 175 CAYAs treated on COG trials for r/r cHL (5.7% Asian or Pacific Islander, 14.9% Hispanic, 14.3% NHB, 61.7% NHW, 3.4% other), at median follow‐up of 4.9 years, 3‐year OS was 82.1% (95% confidence interval [CI], 75.3%–87.1%) and did not differ by race and ethnicity ( p = 0.36). In multivariable analyses, shorter time from diagnosis to relapse trial enrollment ( p = 0.01) and ≥2 relapses (vs. first, p = 0.004) conferred worse OS, with no significant effect of race and ethnicity ( p = 0.43). Conclusion Post‐relapse survival did not differ by race and ethnicity among CAYAs enrolled in COG trials for r/r cHL, suggesting access to clinical trials may mitigate OS disparities.

Summary 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.