Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab

Abstract Background Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In clas...

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Autores principales:	Rosaria De Filippi, Fortunato Morabito, Armando Santoro, Giovanni Tripepi, Francesco D’Alò, Luigi Rigacci, Francesca Ricci, Emanuela Morelli, Pier Luigi Zinzani, Antonio Pinto
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hodgkin lymphoma Immune checkpoint inhibitors Body mass index Immune-related adverse events Medicine R
Acceso en línea:	https://doaj.org/article/f8e8de9a4961465ba54ef26969155fce
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spelling	oai:doaj.org-article:f8e8de9a4961465ba54ef26969155fce2021-12-05T12:05:58ZBody mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab10.1186/s12967-021-03134-41479-5876https://doaj.org/article/f8e8de9a4961465ba54ef26969155fce2021-12-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03134-4https://doaj.org/toc/1479-5876Abstract Background Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. Methods Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions. Results Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. Conclusions In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic ‘equalizers’ counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.Rosaria De FilippiFortunato MorabitoArmando SantoroGiovanni TripepiFrancesco D’AlòLuigi RigacciFrancesca RicciEmanuela MorelliPier Luigi ZinzaniAntonio PintoBMCarticleHodgkin lymphomaImmune checkpoint inhibitorsBody mass indexImmune-related adverse eventsMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hodgkin lymphoma Immune checkpoint inhibitors Body mass index Immune-related adverse events Medicine R
spellingShingle	Hodgkin lymphoma Immune checkpoint inhibitors Body mass index Immune-related adverse events Medicine R Rosaria De Filippi Fortunato Morabito Armando Santoro Giovanni Tripepi Francesco D’Alò Luigi Rigacci Francesca Ricci Emanuela Morelli Pier Luigi Zinzani Antonio Pinto Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
description	Abstract Background Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. Methods Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions. Results Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. Conclusions In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic ‘equalizers’ counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.
format	article
author	Rosaria De Filippi Fortunato Morabito Armando Santoro Giovanni Tripepi Francesco D’Alò Luigi Rigacci Francesca Ricci Emanuela Morelli Pier Luigi Zinzani Antonio Pinto
author_facet	Rosaria De Filippi Fortunato Morabito Armando Santoro Giovanni Tripepi Francesco D’Alò Luigi Rigacci Francesca Ricci Emanuela Morelli Pier Luigi Zinzani Antonio Pinto
author_sort	Rosaria De Filippi
title	Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
title_short	Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
title_full	Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
title_fullStr	Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
title_full_unstemmed	Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
title_sort	body mass index is not associated with survival outcomes and immune-related adverse events in patients with hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f8e8de9a4961465ba54ef26969155fce
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Body mass index is not associated with survival outcomes and immune-related adverse events in patients with Hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab

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