Reducing the Burden of Oncology Chemoradiotherapy and Radiation Exposure From Diagnostic Imaging by Utilizing Targeted Immunotherapy in Children, Adolescents and Young Adults With Hodgkin Lymphoma

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

2022

DOI

10.1002/pbc.29952

Journal Title

Pediatric Blood and Cancer

Department

Pediatrics

Abstract

Background and Aims: Significant chronic health conditions continues to increase over time among pediatric, adolescent, and young adult (CAYA) classical Hodgkin lymphoma (cHL) survivors. Targeting the tumor microenvironment (TME) and tumor-specific antigens is emerging as effective and safe treatments for cHL patients. Recently, we completed a phase 2 trial evaluating the use of antibody-drug conjugate targeting CD30 (brentuximab vedotin, Bv) and regulatory B-cells (rituximab, RTX) to risk-adapted chemotherapy in newly diagnosed cHL CAYA patients. The combination was safe and resulted in significant reduction to toxic chemotherapy and radiation therapy (RT), while keeping superior outcomes (5-year OS/EFS 100%; Hochberg/Cairo, JITC 2022). Adding the checkpoint inhibitor nivolumab to chemoimmunotherapy with RTX + Bv may allow further anthracycline dose reduction and RT in intermediate-/high-risk cHL in CAYA. Methods: This is a multicenter study for patients with intermediateand high-risk cHL. Intermediate-risk cHL patients receive 2 cycles of Bv, doxorubicin, vinblastine, dacarbazine, and RTX (Bv-AVD-R). Rapid early responders (RER) or slow early responders (SER) by FDG-PET scan receive 2 or 4 cycles of Bv, vinblastine, dacarbazine, nivolumab, and RTX (Bv-NVD-R), respectively. High-risk cHL patients receive 2 cycles of Bv-AVD-R. RERs by FDG-PET scan receive 4 cycles of Bv-NVD-R; SERs receive 2 cycles of Bv, nivolumab, doxorubicin, vinblastine, dacarbazine and RTX (Bv-NAVD-R), followed by 4 cycles of Bv-NVD-R. RT will be given to SER patients not achieving CR. Patients age ≥ 3 and ≤ 39 years will be enrolled with a primary objective to assess safety/feasibility of adding nivolumab to chemoimmunotherapy with RTX + Bv in intermediate-/high-risk cHL. Results: Two patients have been enrolled to date and have had no DLT. Accrual is ongoing. Additional results will be presented at the meeting Conclusions: Targeting the TME (regulatory B-cells) and PD1/PD-L1 axis is a promising approach in CAYA with cHL. (NCT05253495).

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