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.
Keywords: CD56; Hodgkin lymphoma; NK cell maturation; autologous & allogeneic transplantation; immune check point; natural killer cells; nivolumab; programmed cell death receptor 1.
Copyright © 2021 Guolo, Minetto, Pesce, Ballerini, Clavio, Cea, Frello, Garibotto, Greppi, Bozzo, Miglino, Passannante, Marcolin, Tedone, Colombo, Mangerini, Bo, Ruzzenenti, Carlier, Serio, Luchetti, Dominietto, Varaldo, Candiani, Agostini, Ravetti, Del Zotto, Marcenaro and Lemoli.