Tumor-specific immune responses and biomarkers in pediatric patients with high-risk Hodgkin lymphoma

Toner K, Renfro LA, Dave H, Pezzella G, Pei Q, Giulino-Roth L, Horton T, Keller FG, Kelly KM, Castellino SM, Bollard CM. Tumor-specific immune responses and biomarkers in pediatric patients with high-risk Hodgkin lymphoma. Blood Adv. 2026 Jan 13;10(1):183-191. doi: 10.1182/bloodadvances.2025016797. PMID: 40990939; PMCID: PMC12805261.

There is an unmet need to examine antitumor 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 soluble CD30 (sCD30), sCD163, and thymus and activation-regulated chemokine (TARC) in relation to event-free survival in patients with cHL. The Children’s Oncology Group (COG) clinical trial AHOD1331 was a randomized phase 3 trial for patients with newly diagnosed high-risk cHL, aged 2 to 21 years, which compared standard chemotherapy and doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) with brentuximab vedotin (Bv) and AVE-PC with response adapted radiation. Our results demonstrate that chemotherapy with or without addition of anti-CD30 antibody-drug conjugate 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 antitumor immune response, which may aid in application of further cellular and immunotherapies targeting cHL. This trial was registered at www.ClinicalTrials.gov as #NCT02166463.