Journal Article

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

Clavio, Marino, Carlier, Paolo, Miglino, Maurizio, Luchetti, Silvia, Agostini, Vanessa, Candiani, Simona, Ravetti, Jean Louis, Bozzo, Matteo, Varaldo, Riccardo, Minetto, Paola, Mangerini, Rosa, Greppi, Marco, Ruzzenenti, Maria Rosaria, Ballerini, Filippo, Serio, Alberto, Dominietto, Alida, Passannante, Monica, Tedone, Elisabetta, Bo, Alessandra, Marcolin, Riccardo, Colombo, Nicoletta, Lemoli, Roberto Massimo, Guolo, Fabio, Pesce, Silvia, Cea, Michele, Del Zotto, Genny, Marcenaro, Emanuela, Garibotto, Matteo, Frello, Michela

2021

Overview

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the “adaptive” NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adolescent / Adoptive Transfer / Adult / Aged / Antibodies / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Antitumor agents / Apheresis / Autografts / Cell Differentiation / Chemotherapy / Cytomegalovirus Infections - complications / Disease-Free Survival / Feasibility Studies / Female / Flow cytometry / Hematopoietic Stem Cell Transplantation / Hodgkin Disease - complications / Hodgkin Disease - drug therapy / Hodgkin Disease - therapy / Hodgkin lymphoma / Hodgkin's lymphoma / Humans / immune check point / Immune checkpoint inhibitors / Immune Checkpoint Inhibitors - therapeutic use / Immunology / Immunotherapy / Killer Cells, Natural - immunology / Lymphocyte Transfusion / Lymphocytes / Lymphoma / Male / Maturation / Medical prognosis / Middle Aged / Natural killer cells / nivolumab / Nivolumab - therapeutic use / NK cell maturation / Patients / programmed cell death receptor 1 / Recurrence / Salvage Therapy / Stem cell transplantation / Transplantation, Autologous / Young Adult