Risk-adapted chemoimmunotherapy using brentuximab vedotin and rituximab in children, adolescents, and young adults with newly diagnosed Hodgkin's lymphoma: a phase II, non-randomized controlled trial.

BACKGROUND: Cure rates for Hodgkin's lymphoma are excellent, but excess short-term and long-term morbidities from treatment remain a concern. Immunotherapy targeting both tumor antigens and the immunosuppressive tumor microenvironment in children, adolescents, and young adults with Hodgkin's lymphoma may improve early response rates and eliminate toxic chemotherapy and radiation, thus minimizing toxicity. We conducted a phase II study to evaluate the safety and overall response rate of brentuximab vedotin and rituximab in combination with risk-adapted chemotherapy in children, adolescents, and young adults with newly diagnosed classic Hodgkin's lymphoma (cHL). METHODS: This is a prospective, phase II, non-randomized, risk-assigned study. Patients were treated and evaluated between 2012 and 2020. Eligible patients were aged ≥1 and ≤30 years old with advanced stage, intermediate-risk, and high-risk newly diagnosed cHL. Patients received four or six cycles of brentuximab vedotin (1.2 mg/kg), doxorubicin (25 mg/m2), vinblastine (6 mg/m2), dacarbazine (375 mg/m2), and rituximab (375 mg/m2). Early response was evaluated following two cycles of therapy. Involved field radiotherapy (IFRT) was restricted to high-risk patients with both bulky disease and slow response or those not in complete response at the end of chemoimmunotherapy. RESULTS: Thirty patients were enrolled, with a median age of 15 years (4-23). There were 18 intermediate-risk and 12 high-risk patients. Toxicities included grade III mucositis (3%), infusion reaction (3%), and peripheral neuropathy (6%). There was a 100% complete response rate on completion of chemoimmunotherapy. Eighteen patients (60%) achieved a rapid early response. Four patients (13%) required IFRT. The 5-year event-free and overall survival rates were 100%, with a median follow-up of 62 months (18-105). CONCLUSIONS: Immunotherapy with brentuximab vedotin, rituximab, and risk-adapted chemotherapy is safe in children, adolescents, and young adults with newly diagnosed cHL. We have demonstrated 100% complete response and 100% event-free and overall survival rates at a median 5-year follow-up, with a significant reduction in use of more toxic chemotherapy and IFRT. A larger cohort is required to confirm these preliminary findings. TRIAL REGISTRATION NUMBER: NCT02398240.