AUTHOR=Guolo Fabio , Minetto Paola , Pesce Silvia , Ballerini Filippo , Clavio Marino , Cea Michele , Frello Michela , Garibotto Matteo , Greppi Marco , Bozzo Matteo , Miglino Maurizio , Passannante Monica , Marcolin Riccardo , Tedone Elisabetta , Colombo Nicoletta , Mangerini Rosa , Bo Alessandra , Ruzzenenti Maria Rosaria , Carlier Paolo , Serio Alberto , Luchetti Silvia , Dominietto Alida , Varaldo Riccardo , Candiani Simona , Agostini Vanessa , Ravetti Jean Louis , Del Zotto Genny , Marcenaro Emanuela , Lemoli Roberto Massimo TITLE=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 JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.753890 DOI=10.3389/fimmu.2021.753890 ISSN=1664-3224 ABSTRACT=

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.