TARGETED IMMUNOTHERAPY IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH NEWLY DIAGNOSED CLASSICAL HODGKIN LYMPHOMA, A SINGLE CENTER EXPERIENCE

Introduction: Despite excellent survival outcomes, significant chronic health conditions occur among pediatric, adolescent, and young adult classical Hodgkin lymphoma (cHL) survivors as a result of current chemotherapy and radiation regimens. Targeting both the tumor microenvironment as well as tumor-specific antigens have been proven to be effective and safe treatments for cHL patients. Here we report on our Hodgkin Lymphoma immunotherapy approach over the past 13 yrs. We have combined the use of the antibody-drug conjugate brentuximab vedotin (Bv) to target reed-sternberg cells along with the anti-CD20 antibody rituximab (RTX) and checkpoint inhibitor nivolumab (N) targeting the immune microenvironment added to risk-adapted chemotherapy in newly diagnosed CAYA cHL patients. This chemoimmunotherapy approach may allow for anthracycline dose reduction and radiation sparing in intermediate and high risk patients.

Methods: All patients received 2 cycles of Bv, doxorubicin, vinblastine, dacarbazine, and RTX (Bv-AVD-R). Early response utilizing FDG-PET scan was performed following 2 cycles of therapy (PET2) with PET2 negativity defined as Deauville score of 1, 2 or 3. Rapid early responders (RER) or slow early responders (SER) received an additional 2 to 6 cycles of treatment based on risk assignment and early response. After our initial protocol completed enrollment, subsequent patients were enrolled on our follow up study evaluating the addition of nivolumab beginning with cycle 3 therapy without further anthracycline (Bv-NVD-R). This limited the total anthracycline dose to 100 mg/m² per patient. Radiation therapy initially was planned for high risk patients with SER and subsequently on our current study only for patients not achieving metabolic CR by FDG-PET at the completion of all therapy.

Results: A total of 48 patients have completed therapy with a median age of 17 years (4–23 years), Thirty four patients received Bv-AVD-R for all cycles and 14 patients have been enrolled on our follow up study receiving Bv-AVD-R followed by Bv-NVD-R. All 48 patients achieved a complete response to therapy for a CR rate of 100%. Early PET2 negativity was achieved in 42 patients (87.5%). Due to excellent rapid response, only four patients have required radiation therapy. The EFS and OS is 100% with a median follow up time of > 90 months (range 4–159 months) (Fig 1). Accrual is ongoing for our current trial. We have completed the nivolumab saftey run in. There have been no unexpected adverse events related to therapy and no dose limiting toxicities with the addition of nivolumab to our immunochemotherapy backbone.

Conclusions: The addition of immunotherapy to a reduced chemotherapy backbone is safe, effective and well tolerated. Targeting the HRS cell as well as the tumor microenvironment and PD1/PD-L1 axis is a promising approach in CAYA with cHL and may allow for reduction in anthracycline and radiation exposure, thus limiting short- and long-term adverse effects.

Research funding declaration: Pediatric Cancer Foundation, Children's Cancer Fund

Keyword: non-Hodgkin (Pediatric, Adolescent, and Young Adult)

No potential sources of conflict of interest.