LAUSR

Introduction: This study regimen is based on theGPOH-HD 2002 study that demonstrated 5-year EFS and OS of 87% and 95% respectively with 6 cycles OEPA/COPDAC and 20-30 Gy IFRT. The subsequent EuroNet-C1 study showed that 30% of high-risk patients achieved an adequate response (AR) after 2 cycles of OEPA and could forgo radiation therapy. To explore if radiation could be reduced further, this study substituted Brentuximab vedotin (Bv) for vincristine in the regimen. Methods: Children≤ 18 years of age, newly diagnosed with stage IIB, IIIB, and IV classical Hodgkin lymphoma were treated with Bv substituting vincristine (AEPA/CAPDac) and 25 Gy ISRT only to areas not in CR at early response evaluation (CR: >75% anatomic response product of 2 perpendicular diameters of lesions by CT and Deauville Score (DS) < 4 on PET). Objectives: To evaluate the safety of AEPA/CAPDac and the efficacy, defined as the number of patients achieving AR when retrospectively applying the Euro-Net C1 criteria (AR: residual tumor volume ≤50% [CT/MRI] and DS < 3 in lesions ≥ 2 cm and DS < 2 in smaller lesions) following 2 cycles of AEPA. Results: 77 patients were enrolled in this multi-institutional trial between 8/2013 and 2/2018 (table). Therapy was well-tolerated with most common adverse events being leukopenia and excessive weight gain. Peripheral neuropathy was rarely reported (mostly grade 2; 3 grade 3). Events included one cardiac death (arrhythmia associated to pancarditis) during therapy and one disease progression in an originally involved site (now disease free > 4 years after retrieval therapy). The first 32 enrolled patients were available for post-hoc EuroNet-C1 response assessment. The proportion of patients achieving AR following AEPA (x2) using the EuroNet-C1 criteria did not differ from that observed after OEPA (x2) in EuroNet C1, TG3 28% versus 30% (90%CI [16; 44]). Conclusions: AEPA/CAPDac is very well tolerated without substantial neurotoxicity. Substitution of vincristine with Bv did not reduce the proportion of individuals receiving radiation compared to EuroNet-C1 trial; however, radiating only sites of inadequate response (less than 1 out of 5 sites) rather than all sites of initial disease reduces the number of sites treated. Additional follow-up is required to determine the sustainability of disease free and overall survival. This is a PI initiated trial, sponsored by Seattle Genetics Inc.