Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events

Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients...

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Veröffentlicht in:	European journal of cancer (1990) 2020-03, Vol.128, p.17-26
Hauptverfasser:	Cortellini, Alessio, Bersanelli, Melissa, Santini, Daniele, Buti, Sebastiano, Tiseo, Marcello, Cannita, Katia, Perrone, Fabiana, Giusti, Raffaele, De Tursi, Michele, Zoratto, Federica, Marconcini, Riccardo, Russano, Marco, Zeppola, Tea, Anesi, Cecilia, Filetti, Marco, Marchetti, Paolo, Botticelli, Andrea, Gelibter, Alain, De Galitiis, Federica, Vitale, Maria Giuseppa, Rastelli, Francesca, Tudini, Marianna, Silva, Rosa Rita, Atzori, Francesco, Chiari, Rita, Ricciuti, Biagio, De Giglio, Andrea, Migliorino, Maria Rita, Mallardo, Domenico, Vanella, Vito, Mosillo, Claudia, Bracarda, Sergio, Rinaldi, Silvia, Berardi, Rossana, Natoli, Clara, Ficorella, Corrado, Porzio, Giampiero, Ascierto, Paolo A.
Format:	Artikel
Sprache:	eng
Schlagworte:	BMI Cancer Checkpoint inhibitors Immune-related adverse events Immunotherapy Obesity Overweight PD-1/PD-L1
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container_title	European journal of cancer (1990)
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creator	Cortellini, Alessio Bersanelli, Melissa Santini, Daniele Buti, Sebastiano Tiseo, Marcello Cannita, Katia Perrone, Fabiana Giusti, Raffaele De Tursi, Michele Zoratto, Federica Marconcini, Riccardo Russano, Marco Zeppola, Tea Anesi, Cecilia Filetti, Marco Marchetti, Paolo Botticelli, Andrea Gelibter, Alain De Galitiis, Federica Vitale, Maria Giuseppa Rastelli, Francesca Tudini, Marianna Silva, Rosa Rita Atzori, Francesco Chiari, Rita Ricciuti, Biagio De Giglio, Andrea Migliorino, Maria Rita Mallardo, Domenico Vanella, Vito Mosillo, Claudia Bracarda, Sergio Rinaldi, Silvia Berardi, Rossana Natoli, Clara Ficorella, Corrado Porzio, Giampiero Ascierto, Paolo A.
description	Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI. One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21–92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6–46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p
doi_str_mv	10.1016/j.ejca.2019.12.031
format	Article
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In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI. One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21–92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6–46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5–14.9 for overweight, and 16.6 (95%CI: 10.3–26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4–22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3–18.2], p < 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients. Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'. •Several studies have found an association between higher BMI and improved outcomes in patients receiving PD-1/PD-L1 checkpoint inhibitors.•The upside of the downside of this obesity paradox, might be the association between BMI and immune-related adverse events (irAEs).•In this large case series, we found a significant association, between BMI and irAEs.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2019.12.031</identifier><identifier>PMID: 32109847</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>BMI ; Cancer ; Checkpoint inhibitors ; Immune-related adverse events ; Immunotherapy ; Obesity ; Overweight ; PD-1/PD-L1</subject><ispartof>European journal of cancer (1990), 2020-03, Vol.128, p.17-26</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-89326d559ad19e1471839073801652388c51ea590d293915ef487875c6d9481f3</citedby><cites>FETCH-LOGICAL-c422t-89326d559ad19e1471839073801652388c51ea590d293915ef487875c6d9481f3</cites><orcidid>0000-0002-0731-5721 ; 0000-0002-1081-5313</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0959804920300046$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32109847$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cortellini, Alessio</creatorcontrib><creatorcontrib>Bersanelli, Melissa</creatorcontrib><creatorcontrib>Santini, Daniele</creatorcontrib><creatorcontrib>Buti, Sebastiano</creatorcontrib><creatorcontrib>Tiseo, Marcello</creatorcontrib><creatorcontrib>Cannita, Katia</creatorcontrib><creatorcontrib>Perrone, Fabiana</creatorcontrib><creatorcontrib>Giusti, Raffaele</creatorcontrib><creatorcontrib>De Tursi, Michele</creatorcontrib><creatorcontrib>Zoratto, Federica</creatorcontrib><creatorcontrib>Marconcini, Riccardo</creatorcontrib><creatorcontrib>Russano, Marco</creatorcontrib><creatorcontrib>Zeppola, Tea</creatorcontrib><creatorcontrib>Anesi, Cecilia</creatorcontrib><creatorcontrib>Filetti, Marco</creatorcontrib><creatorcontrib>Marchetti, Paolo</creatorcontrib><creatorcontrib>Botticelli, Andrea</creatorcontrib><creatorcontrib>Gelibter, Alain</creatorcontrib><creatorcontrib>De Galitiis, Federica</creatorcontrib><creatorcontrib>Vitale, Maria Giuseppa</creatorcontrib><creatorcontrib>Rastelli, Francesca</creatorcontrib><creatorcontrib>Tudini, Marianna</creatorcontrib><creatorcontrib>Silva, Rosa Rita</creatorcontrib><creatorcontrib>Atzori, Francesco</creatorcontrib><creatorcontrib>Chiari, Rita</creatorcontrib><creatorcontrib>Ricciuti, Biagio</creatorcontrib><creatorcontrib>De Giglio, Andrea</creatorcontrib><creatorcontrib>Migliorino, Maria Rita</creatorcontrib><creatorcontrib>Mallardo, Domenico</creatorcontrib><creatorcontrib>Vanella, Vito</creatorcontrib><creatorcontrib>Mosillo, Claudia</creatorcontrib><creatorcontrib>Bracarda, Sergio</creatorcontrib><creatorcontrib>Rinaldi, Silvia</creatorcontrib><creatorcontrib>Berardi, Rossana</creatorcontrib><creatorcontrib>Natoli, Clara</creatorcontrib><creatorcontrib>Ficorella, Corrado</creatorcontrib><creatorcontrib>Porzio, Giampiero</creatorcontrib><creatorcontrib>Ascierto, Paolo A.</creatorcontrib><title>Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI. One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21–92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6–46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5–14.9 for overweight, and 16.6 (95%CI: 10.3–26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4–22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3–18.2], p < 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients. Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'. •Several studies have found an association between higher BMI and improved outcomes in patients receiving PD-1/PD-L1 checkpoint inhibitors.•The upside of the downside of this obesity paradox, might be the association between BMI and immune-related adverse events (irAEs).•In this large case series, we found a significant association, between BMI and irAEs.</description><subject>BMI</subject><subject>Cancer</subject><subject>Checkpoint inhibitors</subject><subject>Immune-related adverse 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Francesco</au><au>Chiari, Rita</au><au>Ricciuti, Biagio</au><au>De Giglio, Andrea</au><au>Migliorino, Maria Rita</au><au>Mallardo, Domenico</au><au>Vanella, Vito</au><au>Mosillo, Claudia</au><au>Bracarda, Sergio</au><au>Rinaldi, Silvia</au><au>Berardi, Rossana</au><au>Natoli, Clara</au><au>Ficorella, Corrado</au><au>Porzio, Giampiero</au><au>Ascierto, Paolo A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>128</volume><spage>17</spage><epage>26</epage><pages>17-26</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI. One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21–92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6–46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5–14.9 for overweight, and 16.6 (95%CI: 10.3–26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4–22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3–18.2], p < 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients. Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'. •Several studies have found an association between higher BMI and improved outcomes in patients receiving PD-1/PD-L1 checkpoint inhibitors.•The upside of the downside of this obesity paradox, might be the association between BMI and immune-related adverse events (irAEs).•In this large case series, we found a significant association, between BMI and irAEs.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32109847</pmid><doi>10.1016/j.ejca.2019.12.031</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0731-5721</orcidid><orcidid>https://orcid.org/0000-0002-1081-5313</orcidid></addata></record>
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issn	0959-8049 1879-0852
language	eng
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source	Elsevier ScienceDirect Journals
subjects	BMI Cancer Checkpoint inhibitors Immune-related adverse events Immunotherapy Obesity Overweight PD-1/PD-L1
title	Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events
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