Frontiers in Immunology (Nov 2021)

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

DOI
https://doi.org/10.3389/fimmu.2021.753890
Journal volume & issue
Vol. 12

Abstract

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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.

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