Excellent Outcome for Pediatric Patients with High Risk Hodgkin Lymphoma with Brentuximab Vedotin and Risk Adapted Residual Node Radiation

Background: Brentuximab vedotin is an anti-CD30 antibody-drug conjugate approved for use in adults with newly diagnosed and relapsed/refractory high-risk classical Hodgkin lymphoma (HL). Methods: Open label, single-arm, multicenter trial for patients (age < 18 years) with stage IIB, IIIB or IV classical HL. One dose of brentuximab vedotin (AdcetrisO) replaced each vincristine in the OEPA [vincristine, etoposide, prednisone, and doxorubicin]/COPDac [cyclophosphamide, vincristine, prednisone, and dacarbazine] regimen (2 cycles of AEPA and 4 cycles of CAPDac) according to GPOH-HD2002 treatment group 3 [TG3]. 1 Residual node radiotherapy (25·5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after 2 cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free and overall survival. Findings: Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3·4 years, the 3 year event-free survival was 97·4% (SE 2·3%) and overall survival 98·7% (SE 1·6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% patients experienced Grade 3 neuropathy. Interpretation: The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated reduction in  radiation exposure, and yielded excellent outcomes. Trial Registration: IND (#118603), The trial is registered with www.clinicaltrials.gov, NCT01920932. Funding Statement: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA021765. Declaration of Interests: None to declare. Ethics Approval Statement: The trial was approved by the institutional review board of each participating center and monitored by the SJCRH Data, Safety, and Monitoring Board. Informed consent was obtained as per institutional guidelines.