Castellino, Sharon

We present a subset analysis on the adolescent cohort of the S1826 randomized phase three trial, comparing nivolumab, doxorubicin, vinblastine, dacarbazine (N-AVD) to brentuximab vedotin-AVD (BV-AVD) in newly diagnosed advanced-stage (AS, stages III and IV) classic Hodgkin lymphoma (cHL). Among 994 patients enrolled, 24% (n = 240) were age 12-17 years. The 3-year progression-free survival (PFS) was significantly higher in the N-AVD group (93% [95% CI, 87 to 96]) compared with the BV-AVD group (82% [95% CI, 73 to 88]; hazard ratio, 0.37 [95% CI, 0.17 to 0.80]). One N-AVD and two BV-AVD patients received protocol-specified residual site radiotherapy (RT). Rates of febrile neutropenia and sepsis were low in both groups. Severe immune-related adverse events were infrequent, although thyroid dysfunction was seen in 7% with N-AVD. Sensory neuropathy (grade ≥2) was more frequent with BV-AVD (14% v 7%) by clinician report. Although premature discontinuation of therapy was reported in 12 N-AVD patients and four BV-AVD patients, no PFS events were noted in the N-AVD group. Patient-reported outcomes indicated less toxicity with N-AVD. N-AVD demonstrated high 3-year PFS in adolescents with AS cHL, with minimal RT use. S1826 exemplifies the benefits of harmonized clinical trial protocols, resulting in timely access to novel agents for adolescents.

PURPOSE Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy is used commonly for pediatric Hodgkin lymphoma (pHL) in low- and middle-income countries. The role of radiotherapy (RT) after ABVD in pHL is uncertain. MATERIALS AND METHODS We conducted a systematic review to explore the use of ABVD with or without RT in pHL. Key clinical questions included the number of cycles of ABVD, indications for and dose of RT, and outcomes by risk group. A search was performed in PubMed. Articles reporting survival outcomes by risk group were included. RESULTS Of 97 articles identified in the literature search, nine met inclusion criteria. Chemotherapy consisted of four to six cycles in limited disease and mostly six cycles in advanced disease. Three studies used RT for all patients within a specified risk group. Six studies dictated an adapted RT approach, with 3%-43% of the patients receiving RT for bulky adenopathy, slow early response (SER), and/or incomplete response. Radiation doses ranged between 20 and 36 Gy. The progression-free survival and overall survival at 4-10 years ranged from 84% to 100% and 93%-100% in limited disease and 50%-84.4% and 75%-95.3% in advanced disease, respectively. Studies did not directly assess the impact of certain chemotherapy or RT strategies. Recommendations were made after reviewing outcomes with particular approaches. CONCLUSION Four cycles of ABVD are recommended for limited disease, and six cycles of ABVD are recommended for advanced disease. In both limited and advanced diseases, RT is recommended with a dose of 20-21 Gy only to sites of bulky and/or SER, with a boost of up to 36 Gy to sites of incomplete response. This approach could spare radiation for at least half of the patients with limited disease and one third of advanced disease.

AbstractThe goal of therapy in pediatric Hodgkin lymphoma (HL) is to maximize overall survival while minimizing the morbidity of curative therapy. Key findings from recent Children's Oncology Group (COG) trials include: (i) superior event‐free survival with the addition of brentuximab vedotin (Bv) in frontline regimens for high‐risk disease, (ii) successful reduction in myeloablative regimens with demonstrated safety and efficacy of Bv and checkpoint inhibitor therapy in relapsed disease, and (ii) the potential to select a population that can be salvaged after relapse without receiving a stem cell transplant. The COG HL committee will lead a National cancer Institute National Clinical Trials Network phase 3 trial to evaluate the combination of Bv/nivolumab in early‐stage disease. Ongoing advances in technology and blood biomarkers are increasing the ability to deliver biologically driven, personalized treatment for HL.