Tumor-Specific Immune Responses and Biomarkers in pediatric High-Risk Hodgkin Lymphoma Patients Open Access

• Tumor-specific T cell immune response to antigen PRAME increases post treatment for pediatric high-risk Hodgkin Lymphoma

• Immunosuppressive cytokines decrease post treatment potentially influencing future addition of immunotherapy for pediatric Hodgkin Lymphoma

There is an unmet need to examine anti-tumor immune responses and predictive biomarkers in the peripheral blood to guide effective combination immunotherapies in classical Hodgkin Lymphoma (cHL). We sought to evaluate T cell specific immune responses as well as cytokine and chemokine profiles including levels of sCD30, sCD163 and TARC in relation to event-free survival (EFS) in patients with cHL. The Children's Oncology Group clinical trial AHOD1331 (NCT02166463) was a randomized phase III trial for patients with newly diagnosed high risk cHL ages 2 to 21 years which compared standard chemotherapy with doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC) to brentuximab vedotin (Bv) + AVE-PC with response adapted radiation. Our results demonstrate that chemotherapy with or without addition of anti-CD30 antibody drug conjugate brentuximab vedotin (Bv) is associated with a favorable cytokine environment for cellular and immunotherapies. Treatment of cHL on both arms increased tumor antigen-specific T cell responses and resulted in decreased levels of sCD30, sCD163 and TARC. We demonstrate that treatment of cHL on COG AHOD1331 produced an environment that favors anti-tumor immune response, which may aid in application of further cellular and immunotherapies targeting cHL.