90 Y-Daclizumab (Anti-CD25), High-Dose Carmustine, Etoposide, Cytarabine, and Melphalan Chemotherapy and Autologous Hematopoietic Stem Cell Transplant Yielded Sustained Complete Remissions in 4 Patients with Recurrent Hodgkin’s Lymphoma

Background: Despite advances in therapy of Hodgkin’s lymphoma (HL), a proportion of patients will not respond or relapse. The authors had previously identified CD25, IL-2R a , as a target for systemic radioimmunotherapy of HL since most normal cells do not express CD25, but it is expressed by a minority of Hodgkin/Reed-Sternberg (HRS) cells and most Tregs rosetting around HRS cells. Study Design and Treatment: This was a single institution, nonrandomized, open-label phase I/II trial of radiolabeled 90 Y-daclizumab, an anti-CD25 monoclonal antibody, BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning treatment followed by autologous hematopoietic stem cell transplant (ASCT). Four patients with refractory and relapsed HL were treated in this trial with 3 patients receiving a single dose of 564.6–574.6 MBq 90 Y-daclizumab and the fourth patient receiving two doses of 580.9–566.1 MBq 90 Y-daclizumab followed by high-dose chemotherapy and ASCT. Results: All 4 evaluable patients treated with 90 Y-daclizumab regimen for refractory and relapsed HL patients with high-dose BEAM chemotherapy and ASCT provided sustained CRs in the 4 patients studied. Two of these patients were highly refractory to multiple prior treatments with bulky disease at entry into this study, including 1 patient who never entered a remission and had failed 6 different therapeutic regimens. Despite the small number of patients treated in this study, the sustained clinical benefit in these patients indicates a highly effective treatment. The daclizumab was directed primarily not at HRS cells themselves but toward nonmalignant T cells rosetting around malignant cells. 90 Y provided strong b emissions that killed antigen nonexpressing tumor cells at a distance by a crossfire effect. Furthermore, the strong b radiation killed normal cells in the tumor microenvironment that nurtured the malignant cells in the lymphomatous mass. The present study supports expanded analysis of 90 Y-daclizumab as part of the regimen of ASCT in patients with refractory and relapsed HL. Follow- up uptake PD-1, ligands, PD-L1, and PD-L2 and promote their induction through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. 39 PD-1 blockade with nivolumab in relapsed or refractory HL of 23 studied patients after relapse following autologous stem cell transplantation and/or following receipt of brentuximab vedotin was associated with an objective response in 27 patients (87%), including 17% with a CR and 70% with a PR. 11