Background Significant chronic health conditions continue 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 are emerging as effective and safe treatments for cHL patients which may help reduce toxicity. Recently, we completed a phase 2 trial evaluating the use of an antibody-drug conjugate targeting CD30 (brentuximab vedotin, Bv) and an anti-CD20 antibody targeting regulatory B-cells (rituximab, RTX) added 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%).1 Adding the checkpoint inhibitor nivolumab to chemoimmunotherapy with RTX + Bv may allow further anthracycline dose reduction and reduce the need for RT in intermediate-/high-risk cHL in CAYA.
Methods This is a multicenter study for patients with intermediate- and high-risk cHL. Intermediate-risk cHL patients receive 2 cycles of Bv, doxorubicin, vinblastine, dacarbazine, and RTX (Bv-AVD-R). Rapid early responders (RER, complete metabolic response) or slow early responders (SER, incomplete metabolic response) by FDG-PET interim scan receive 2 or 4 cycles of Bv, vinblastine, dacarbazine, nivolumab, and RTX (Bv-NVD-R), respectively without further anthracycline. 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 only be given to patients not achieving complete remission (CR) at the end of therapy.
Results Twelve patients have been enrolled to date including 5 intermediate- and 7 high-risk patients. Three intermediate- and 5 high-risk patients have completed interim imaging studies. All intermediate-risk patients and 3 high risk patients have achieved a CR (RER). Two high-risk patients had a partial response (SER). Both SER patients achieved a CR following the 6 additional cycles of chemotherapy as detailed above. No patients have required radiation therapy. There have been no dose limiting toxicities. Accrual is ongoing.
Conclusions Targeting the Hodgkin Reed-Sternberg cell as well as the TME (regulatory B-cells) and PD1/PD-L1 axis is a promising approach in CAYA with cHL. (NCT05253495).
Trial Registration Clinicaltrials.gov, NCT05253495
Hochberg J, Basso J, Shi Q, Klejmont L, Flower A, Bortfeld K, Harrison L, van de Ven C, Moorthy C, Islam H, Gerard P, Voss S, Cairo MS. Risk-adapted chemoimmunotherapy using brentuximab vedotin and rituximab in children, adolescents, and young adults with newly diagnosed Hodgkin’s lymphoma: a phase II, non-randomized controlled trial. J. Immunother. Cancer. 2022;10:e004445.
Ethics Approval This study was approved by New York Medical College’s Ethics Board; approval number 14601.
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