Adoptive Cell Therapy and Immune Check Points Inhibitors As a Salvage Treatment for Patient Affected By Relapsed/Refractory Hodgkin's Lymphoma

BACKROUND: Hodgkin Lymphoma (HL) is characterized by a high degree of response to chemotherapy and an overall favorable outcome in responding patients. Despite the efficacy of first line therapy, however, about 30% of patients affected by HL eventually relapse or are refractory (R/R) to first or second line therapy followed by autologous hemopoietic stem cell transplantation (ASCT). Recently, the clinical application of immune checkpoint inhibitors (CI), in particular the PD-1 targeting antibody Nivolumab, has dramatically improved the prognosis of patients affected by advanced phase solid tumours. In HL, Nivolumab has shown good activity in the difficult setting of patients relapsing after ASCT; however, complete response (CR) rate was less than 20%. Many studies in the solid tumours field have shown that the efficacy of CI is strictly related to the host degree of immune competence, which is greatly impaired in heavily pre-treated HL patients who received ASCT. Therefore, there is a strong rationale in enhancing the activity of the CI with the co-infusion of autologous lymphocytes (ALI), that have been collected in the early phase of therapy, and that are functionally activated. AIMS OF THE STUDY: Primary endpoint of this prospective trial was the evaluation of the efficacy of ALI in combination with pre-emptive CI administration early post ASCT in patients affected by R/R HL. Secondary pre-clinical endpoint was the study of the peripheral blood lymphocyte subpopulation, pre and post adoptive immune cell therapy and CI administration. METHODS: HL patients under the age of 60 with active R/R disease who have already failed at least two chemotherapy lines and Brentuximab (BV) were eligible for the trial. All enrolled patient underwent early lymphocyte apheresis, with a target cell dose of 5x107 CD3+/kg. All patients then received ASCT with FEAM conditioning. After ASCT, the first ALI was delivered 7 days after engraftment. ALI dosing was incremental, one logarithm at each step, starting from 1x104/kg in the first infusion to a maximum of 1x107/kg in the fourth and last infusion. Each ALI was followed after 48 hours by the administration of Nivolumab 240 mg flat dose. The second ALI dose was administered at 14 days after the first one. The third and the fourth were given every 21 days. Lymphocyte subpopulations were extensively studied on peripheral blood samples before and after each ALI and each Nivolumab administration, by 8-colours flow cytometry. Clini