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

Keri Toner, Center for Cancer and Immunology Research Children's National Hospital; and Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.
Lindsay A. Renfro, Division of Biostatistics, University of Southern California and Children's Oncology Group, Los Angeles, CA.
Hema Dave, Center for Cancer and Immunology Research Children's National Hospital; and Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.
Gloria Pezzella, Center for Cancer and Immunology Research Children's National Hospital; and Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.
Qinglin Pei, Department of Biostatistics, University of Florida, Gainesville, FL.
Lisa Giulino-Roth, Department of Pediatrics, Weill Cornell Medical College, New York, NY.
Terzah Horton, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Frank G. Keller, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta/Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
Kara M. Kelly, Roswell Park Comprehensive Cancer Center/Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY.
Sharon M. Castellino, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta/Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
Catherine M. Bollard, Center for Cancer and Immunology Research Children's National Hospital; and Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.

Document Type

Journal Article

Publication Date

1-13-2026

Journal

Blood advances

Volume

10

Issue

1

DOI

10.1182/bloodadvances.2025016797

Abstract

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.

Department

Pediatrics

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