{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T10:17:25Z","timestamp":1771064245250,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["IRCCS"],"award-info":[{"award-number":["IRCCS"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)\/PD-ligand-1<jats:bold>(<\/jats:bold>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015\u2013December 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\u2013Meier method, landmark-analyses and Cox regressions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Patients, mostly males (63%, n\u2009=\u200984) with a median age of 35\u00a0years (range, 15\u201382), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1\u20139), received a median of 18 nivolumab doses (range, 1\u201357). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n\u2009=\u200966; 49.6%) and overweight (n\u2009=\u200931; 23.3%) patients. Underweight (n\u2009=\u200912; 9%) and obese (n\u2009=\u200924; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P\u2009=\u20090.5) or categorical (P for trend\u2009=\u20090.63) 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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 \u2018equalizers\u2019 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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-021-03134-4","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T10:03:02Z","timestamp":1638352982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"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"],"prefix":"10.1186","volume":"19","author":[{"given":"Rosaria","family":"De Filippi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fortunato","family":"Morabito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armando","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Tripepi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"D\u2019Al\u00f2","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Rigacci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Luigi","family":"Zinzani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-9026","authenticated-orcid":false,"given":"Antonio","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"3134_CR1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41591-018-0221-5","volume":"25","author":"Z Wang","year":"2019","unstructured":"Wang Z, Aguilar EG, Luna JI, et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med. 2019;25:141\u201351. https:\/\/doi.org\/10.1038\/s41591-018-0221-5.","journal-title":"Nat Med"},{"key":"3134_CR2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s40425-019-0527-y","volume":"7","author":"A Cortellini","year":"2019","unstructured":"Cortellini A, Bersanelli M, Buti S, et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1\/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. J Immunother Cancer. 2019;7:57. https:\/\/doi.org\/10.1186\/s40425-019-0527-y.","journal-title":"J Immunother Cancer"},{"key":"3134_CR3","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1007\/s00262-020-02680-y","volume":"69","author":"H Chen","year":"2020","unstructured":"Chen H, Wang D, Zhong Q, et al. Pretreatment body mass index and clinical outcomes in cancer patients following immune checkpoint inhibitors: a systematic review and meta-analysis. Cancer Immunol Immunother. 2020;69:2413\u201324. https:\/\/doi.org\/10.1007\/s00262-020-02680-y.","journal-title":"Cancer Immunol Immunother"},{"key":"3134_CR4","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ejca.2018.10.014","volume":"109","author":"J Rogado","year":"2019","unstructured":"Rogado J, S\u00e1nchez-Torres JM, Romero-Laorden N, et al. Immune-related adverse events predict the therapeutic efficacy of anti-PD-1 antibodies in cancer patients. Eur J Cancer. 2019;109:21\u20137. https:\/\/doi.org\/10.1016\/j.ejca.2018.10.014.","journal-title":"Eur J Cancer"},{"key":"3134_CR5","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ejca.2019.12.031","volume":"128","author":"A Cortellini","year":"2020","unstructured":"Cortellini A, Bersanelli M, Santini D, et al. 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. Eur J Cancer. 2020;128:17\u201326. https:\/\/doi.org\/10.1016\/j.ejca.2019.12.031.","journal-title":"Eur J Cancer"},{"key":"3134_CR6","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1001\/jamaoncol.2019.5241","volume":"6","author":"G Kichenadasse","year":"2020","unstructured":"Kichenadasse G, Miners JO, Mangoni AA, et al. Association between body mass index and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer. JAMA Oncol. 2020;6:512\u20138. https:\/\/doi.org\/10.1001\/jamaoncol.2019.5241.","journal-title":"JAMA Oncol"},{"key":"3134_CR7","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1200\/JCO.2017.76.0793","volume":"36","author":"P Armand","year":"2018","unstructured":"Armand P, Engert A, Younes A, et al. Nivolumab for relapsed\/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 trial. J Clin Oncol. 2018;36:1428\u201339. https:\/\/doi.org\/10.1200\/JCO.2017.76.0793.","journal-title":"J Clin Oncol"},{"key":"3134_CR8","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1200\/JCO.2017.77.3994","volume":"36","author":"MGM Roemer","year":"2018","unstructured":"Roemer MGM, Redd RA, Cader FZ, et al. Major histocompatibility complex class II and programmed death ligand 1 expression predict outcome after programmed death 1 blockade in classic Hodgkin lymphoma. J Clin Oncol. 2018;36:942\u201350. https:\/\/doi.org\/10.1200\/JCO.2017.77.3994.","journal-title":"J Clin Oncol"},{"key":"3134_CR9","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1200\/JCO.2016.66.4482","volume":"34","author":"MG Roemer","year":"2016","unstructured":"Roemer MG, Advani RH, Ligon AH, et al. PDL1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol. 2016;34:2690\u20137. https:\/\/doi.org\/10.1200\/JCO.2016.66.4482.","journal-title":"J Clin Oncol"},{"key":"3134_CR10","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800homa","volume":"32","author":"BD Cheson","year":"2014","unstructured":"Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymp: the Lugano classification. J Clin Oncol. 2014;32:3059\u201368. https:\/\/doi.org\/10.1200\/JCO.2013.54.8800homa.","journal-title":"J Clin Oncol"},{"key":"3134_CR11","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s40425-017-0300-z","volume":"5","author":"I Puzanov","year":"2017","unstructured":"Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5:95. https:\/\/doi.org\/10.1186\/s40425-017-0300-z.","journal-title":"J Immunother Cancer"},{"key":"3134_CR12","doi-asserted-by":"publisher","first-page":"c255","DOI":"10.1159\/000328916","volume":"119","author":"VS Stel","year":"2011","unstructured":"Stel VS, Dekker FW, Tripepi G, et al. Survival analysis II: cox regression. Nephron Clin Pract. 2011;119:c255\u201360. https:\/\/doi.org\/10.1159\/000328916.","journal-title":"Nephron Clin Pract"},{"issue":"26","key":"3134_CR13","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s12350-019-01624-z","volume":"2019","author":"CJ Morgan","year":"2019","unstructured":"Morgan CJ. Landmark analysis: a primer. J Nucl Cardiol. 2019;2019(26):391\u20133. https:\/\/doi.org\/10.1007\/s12350-019-01624-z.","journal-title":"J Nucl Cardiol"},{"key":"3134_CR14","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s40425-019-0512-5","volume":"7","author":"GS Naik","year":"2019","unstructured":"Naik GS, Waikar SS, Johnson AEW, et al. Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition. J Immunother Cancer. 2019;7:89. https:\/\/doi.org\/10.1186\/s40425-019-0512-5.","journal-title":"J Immunother Cancer"},{"key":"3134_CR15","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s40425-019-0699-5","volume":"7","author":"D Donnelly","year":"2019","unstructured":"Donnelly D, Bajaj S, Yu J, et al. The complex relationship between body mass index and response to immune checkpoint inhibition in metastatic melanoma patients. J Immunother Cancer. 2019;7:222. https:\/\/doi.org\/10.1186\/s40425-019-0699-5.","journal-title":"J Immunother Cancer"},{"key":"3134_CR16","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.lungcan.2019.11.011","volume":"139","author":"E Ichihara","year":"2020","unstructured":"Ichihara E, Harada D, Inoue K, et al. The impact of body mass index on the efficacy of anti-PD-1\/PD-L1 antibodies in patients with non-small cell lung cancer. Lung Cancer. 2020;139:140\u20135. https:\/\/doi.org\/10.1016\/j.lungcan.2019.11.011.","journal-title":"Lung Cancer"},{"key":"3134_CR17","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001403","volume":"8","author":"A Cortellini","year":"2020","unstructured":"Cortellini A, Ricciuti B, Tiseo M, et al. Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression \u2265 50%: a multicenter study with external validation. J Immunother Cancer. 2020;8: e001403. https:\/\/doi.org\/10.1136\/jitc-2020-001403.","journal-title":"J Immunother Cancer"},{"key":"3134_CR18","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.coi.2018.03.012","volume":"51","author":"EG Aguilar","year":"2018","unstructured":"Aguilar EG, Murphy WJ. Obesity induced T cell dysfunction and implications for cancer immunotherapy. Curr Opin Immunol. 2018;51:181\u20136. https:\/\/doi.org\/10.1016\/j.coi.2018.03.012.","journal-title":"Curr Opin Immunol"},{"key":"3134_CR19","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1002\/path.2711","volume":"221","author":"D Aldinucci","year":"2010","unstructured":"Aldinucci D, Gloghini A, Pinto A, et al. The classical Hodgkin\u2019s lymphoma microenvironment and its role in promoting tumour growth and immune escape. J Pathol. 2010;221:248\u201363. https:\/\/doi.org\/10.1002\/path.2711.","journal-title":"J Pathol"},{"key":"3134_CR20","doi-asserted-by":"publisher","first-page":"6812","DOI":"10.1158\/1078-0432.CCR-13-1879","volume":"19","author":"PR Marri","year":"2013","unstructured":"Marri PR, Hodge LS, Maurer MJ, et al. Prognostic significance of pretreatment serum cytokines in classical Hodgkin lymphoma. Clin Cancer Res. 2013;19:6812\u20139. https:\/\/doi.org\/10.1158\/1078-0432.CCR-13-1879.","journal-title":"Clin Cancer Res"},{"key":"3134_CR21","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000725","volume":"8","author":"SK Boi","year":"2020","unstructured":"Boi SK, Orlandella RM, Gibson JT, et al. Obesity diminishes response to PD-1-based immunotherapies in renal cancer. J Immunother Cancer. 2020;8: e000725. https:\/\/doi.org\/10.1136\/jitc-2020-000725.","journal-title":"J Immunother Cancer"},{"key":"3134_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138747","volume":"10","author":"E Oelmann","year":"2015","unstructured":"Oelmann E, Stein H, Berdel WE, et al. Expression of interleukin-1 and interleukin-1 receptors type 1 and type 2 in Hodgkin lymphoma. PLoS ONE. 2015;10: e0138747. https:\/\/doi.org\/10.1371\/journal.pone.0138747.","journal-title":"PLoS ONE"},{"key":"3134_CR23","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1182\/blood.2020008553","volume":"136","author":"S Reinke","year":"2020","unstructured":"Reinke S, Br\u00f6ckelmann PJ, Iaccarino I, et al. Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1. Blood. 2020;136:2851\u201363. https:\/\/doi.org\/10.1182\/blood.2020008553.","journal-title":"Blood"},{"key":"3134_CR24","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001460","volume":"9","author":"X Liu","year":"2021","unstructured":"Liu X, Hogg GD, DeNardo DG. Rethinking immune checkpoint blockade: \u201cbeyond the T cell.\u201d J Immunother Cancer. 2021;9: e001460. https:\/\/doi.org\/10.1136\/jitc-2020-001460.","journal-title":"J Immunother Cancer"},{"key":"3134_CR25","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000821","volume":"8","author":"AC Young","year":"2020","unstructured":"Young AC, Quach HT, Song H, et al. Impact of body composition on outcomes from anti-PD1 +\/- anti-CTLA-4 treatment in melanoma. J Immunother Cancer. 2020;8: e000821. https:\/\/doi.org\/10.1136\/jitc-2020-000821.","journal-title":"J Immunother Cancer"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-021-03134-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-021-03134-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-021-03134-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T10:10:33Z","timestamp":1638353433000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-021-03134-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3134"],"URL":"https:\/\/doi.org\/10.1186\/s12967-021-03134-4","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"21 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients provided written, informed consent to treatment. The procedures followed were in accordance with the precepts of good clinical practice and the declaration of Helsinki. The study was conducted within the INTHEMA protocol (IRSTB100, L3P2065) approved by local ethical committees of coordinating centers.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Rosaria De Filippi has shared patent applications with EDO-Mundipharma irrelevant to the present research. Armando Santoro declares honoraria from Bristol Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Takeda, Roche, Abbvie, Amgen, Celgene, Arqule, Lilly, Sandoz, and Novartis; all irrelevant to the present research. Luigi Rigacci declares honoraria from Merck Sharp & Dohme and Bristol-Myers Squibb; all irrelevant to the present research. Pier Luigi Zinzani declares honoraria from Verastem, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, MERCK Sharp & Dohme, TG Thera, Takeda, Roche, Eusapharma, Kyowa-Kirin, Novartis, ADC-Therapeutics, Incyte, Beigene; all irrelevant to the present research. Antonio Pinto declares honoraria from BRISTOL-Myers Squibb, F. Hoffmann-La Roche, Helssin Healthcare, Janssen, Celgene, Gilead Sciences, Incyte, Servier, Merck Sharp & Dohme and Takeda; all irrelevant to the present research. All the other authors have no conflict of interests to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"489"}}