Durability Results of Treatment with Brentuximab Vedotin in Combination with Nivolumab in Patient with Relapsed or Refractory Hodgkin Lymphoma

Hodgkin’s lymphoma (HL) is a disease that represents approximately 10% of lymphomas with bimodal age distribution. It is curable in approximately 75 percent of patients worldwide. ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) was originally developed for patients with disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), but subsequently became the gold standard initial chemotherapy for patients with HL. Anthracyclines remain as a backbone for combination regimens and in patients with systolic dysfunction MOPP regimen has been used as initial chemotherapy. In patients with relapsed or refractory HL, the goal of treatment should be to achieve long-term disease control and requires salvage regimens to reduce disease burden beforehand followed by autologous hematopoietic cell transplantation (HCT) in curative intent. There are no randomized trials that directly compare the various salvage regimens for relapsed HL. Brentuximab Vedontin (BV) and nivolumab are currently approved for the treatment of refractory disease in patients who have failed two or more first-line treatments or who have failed HCT. Little literature exists regarding the efficacy and overall survival of patients who receive BV with or without nivolumab for refractory disease in patients who are ineligible or refuse HCT. We report a case of a 24-year-old refractory nodular sclerosing Hodgkin’s disease with a lengthy progression-free survival on BV and Nivolumab and without HCT. The patient was diagnosed with stage IV HL due to bone marrow involvement and was started on the MOPP regimen due to an ejection fraction of 45-50% and given a history of transposition of great vessels. The first surveillance PET scan after 6 cycles of MOPP chemotherapy showed new hypermetabolic widespread adenopathy and new multifocal abnormal FDG uptake within the liver and spleen suggestive of early relapse. Salvage chemoimmunotherapy with RICE was then started with the intention to reduce the disease burden prior to HCT. Despite starting salvage chemoimmunotherapy, the patient’s liver function tests (LFT) continued to rise along with progressively worsening pancytopenia. Due to concern for refractoriness and worsening LFT’s, he was started on third-line single-agent nivolumab and showed tremendous response after 4 cycles. BV was added to nivolumab to further improve responses based on phase 2 data. Despite considerable efforts in counseling regarding smoking cessation, he continued to smoke and refused HCT. The patient received 4 cycles of Nivolumab every 2 weeks and then a combination of BV and Nivolumab for 17 cycles. Subsequently had progressive disease. Right, mandibular gingiva biopsy was consistent with high-grade large B cell lymphoma with concern for Richter\u27s transformation from Hodgkin’s to non-Hodgkin’s lymphoma (NHL). He has received a course of radiation therapy to the involved facial area for symptom control and was later started on CEOP (vincristine, etoposide, cyclophosphamide, prednisone) regimen with intrathecal methotrexate. This case provides unique clinical data of durability results of a patient treated with BV in combination with nivolumab in relapsed or refractory HL patients who are ineligible or refuse HCT. Our patient likely had Richter\u27s transformation of HL to the NHL, which has rarely been reported in the literature