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Clinical Trial
. 2026 Jan 13;10(1):183-191.
doi: 10.1182/bloodadvances.2025016797.

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

Keri Toner  1 , Lindsay A Renfro  2 , Hema Dave  1 , Gloria Pezzella  1 , Qinglin Pei  3 , Lisa Giulino-Roth  4 , Terzah Horton  5 , Frank G Keller  6 , Kara M Kelly  7 , Sharon M Castellino  6 , Catherine M Bollard  1
Affiliations
Clinical Trial

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

Keri Toner et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: L.G.-R. serves on an advisory board for Merck; and serves as an adviser to Roche. C.M.B. was a scientific cofounder of Mana Therapeutics and Catamaran Bio; is a current board member of Cabaletta Bio; holds stock in Neximmune and Repertoire Immune Medicines; serves on the Scientific Advisory Board of Minovia Therapeutics Ltd; and serves on the data and safety monitoring board for Sobi. S.M.C. serves on a pediatric advisory board for Seagen Inc (now Pfizer) and Bristol Meyers Squibb. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Tumor-specific T cell response in response to tumor antigens MAGE-A4, PRAME and Survivin. T cell specificity to MAGE-A4 , PRAME, and Survivin both at baseline and post-therapy across both treatment arms (A) as measured by ELISpot in IFNγ SFC/100,000 cells (total n =144 and 72 per treatment arm) and (B) split by treatment arms (but due to numbers, without statistical relevance).
Figure 2.
Figure 2.
sCD30, sCD163, and TARC measured at baseline (before) and after therapy. sCD30 (A), sCD163 (B), and TARC (C) measured by enzyme-linked immunosorbent assay at baseline and after therapy in both chemotherapy arm and chemotherapy with addition of Bv. ns, not significant.
Figure 3.
Figure 3.
Chemokine Pre-treatment values and EFS. Risk of EFS event as a function of pretreatment marker values for sCD30 (A), sCD163 (B), and TARC (C). HR, hazard ratio.
Figure 4.
Figure 4.
Change in chemokines and EFS. Risk of posttreatment EFS event as a function of marker change from before treatment to after treatment for sCD30 (A), sCD163 (B), and TARC (C). HR, hazard ratio.
See this image and copyright information in PMC

References

    1. Castellino SM, Giulino-Roth L, Harker-Murray P, et al. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023;70(suppl 6)
    1. Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin with chemotherapy in pediatric high-risk Hodgkin's lymphoma. N Engl J Med. 2022;387(18):1649–1660. - PMC - PubMed
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