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
Affiliations
- Fabio Guolo
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Fabio Guolo
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- Paola Minetto
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Silvia Pesce
- Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy
- Filippo Ballerini
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Marino Clavio
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Michele Cea
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Michele Cea
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- Michela Frello
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- Matteo Garibotto
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- Marco Greppi
- Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy
- Matteo Bozzo
- Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy
- Matteo Bozzo
- Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Genoa, Italy
- Maurizio Miglino
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Maurizio Miglino
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- Monica Passannante
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- Riccardo Marcolin
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- Elisabetta Tedone
- PathologIcal Anatomy and Histology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Nicoletta Colombo
- PathologIcal Anatomy and Histology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Rosa Mangerini
- PathologIcal Anatomy and Histology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Alessandra Bo
- Stem Cell Processing Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Maria Rosaria Ruzzenenti
- Blood Transfusion Service and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Paolo Carlier
- Blood Transfusion Service and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Alberto Serio
- Stem Cell Processing Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Silvia Luchetti
- Stem Cell Processing Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Alida Dominietto
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Riccardo Varaldo
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Simona Candiani
- Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Genoa, Italy
- Vanessa Agostini
- Blood Transfusion Service and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Jean Louis Ravetti
- PathologIcal Anatomy and Histology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Genny Del Zotto
- Core Facilities, Area Aggregazione Sevizi e Laboratori Diagnostici, IRCCS Giannina Gaslini, Genoa, Italy
- Emanuela Marcenaro
- Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy
- Roberto Massimo Lemoli
- Department of Oncology and Hematology (DIPOE), IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Roberto Massimo Lemoli
- Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa, Genoa, Italy
- DOI
- https://doi.org/10.3389/fimmu.2021.753890
- Journal volume & issue
-
Vol. 12
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.
Keywords
- Hodgkin lymphoma
- nivolumab
- natural killer cells
- programmed cell death receptor 1
- NK cell maturation
- immune check point
