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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number753890
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - Nov 5 2021

Keywords

  • autologous & allogeneic transplantation
  • CD56
  • Hodgkin lymphoma
  • immune check point
  • natural killer cells
  • nivolumab
  • NK cell maturation
  • programmed cell death receptor 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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