{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:50:23Z","timestamp":1773881423621,"version":"3.50.1"},"reference-count":73,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,5,30]],"date-time":"2016-05-30T00:00:00Z","timestamp":1464566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pembrolizumab is a humanized monoclonal antibody directed against programmed cell death protein 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101), a key immune\u2010inhibitory molecule expressed on T cells and implicated in <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4+ T\u2010cell exhaustion and tumor immune\u2010escape mechanisms. Classical Hodgkin's lymphoma (c<jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>) is a unique <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\u2010cell malignancy in the sense that malignant Reed\u2013Sternberg (<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>) cells represent a small percentage of cells within an extensive immune cell infiltrate. <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 ligands are upregulated on <jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> cells as a consequence of both chromosome 9p24.1 amplification and Epstein\u2013Barr virus infection and by interacting with <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 promote an immune\u2010suppressive effect. By augmenting antitumor immune response, pembrolizumab and nivolumab, another monoclonal antibody against <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101, have shown significant activity in patients with relapsed\/refractory c<jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content> as well as an acceptable toxicity profile with immune\u2010related adverse events that are generally manageable. In this review, we explore the rationale for targeting <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 in c<jats:styled-content style=\"fixed-case\">HL<\/jats:styled-content>, review the clinical trial results supporting the use of checkpoint inhibitors in this disease, and present future directions for investigation in which this approach may be used.<\/jats:p>","DOI":"10.1111\/ejh.12770","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T07:46:25Z","timestamp":1462434385000},"page":"219-227","source":"Crossref","is-referenced-by-count":28,"title":["Pembrolizumab in classical Hodgkin's lymphoma"],"prefix":"10.1111","volume":"97","author":[{"given":"Joseph","family":"Maly","sequence":"first","affiliation":[{"name":"Division of Hematology Department of Internal Medicine Arthur G James Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lapo","family":"Alinari","sequence":"additional","affiliation":[{"name":"Division of Hematology Department of Internal Medicine Arthur G James Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,5,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2542"},{"key":"e_1_2_9_3_1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow S","year":"2008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.03.023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa064601"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.43.4803"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.9549"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.3.801"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4689"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu387"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)92411-L"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08938-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704214"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705977"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-253856"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-098483"},{"key":"e_1_2_9_17_1","article-title":"Myeloablative versus reduced intensity allogeneic stem cell transplantation in relapsed Hodgkin's lymphoma in recent years. A retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation","author":"Stavrik SGG","year":"2014","journal-title":"Blood"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-362475"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9588-y"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21664"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.022"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.13.2615"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.2.584"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1069(199809)16:3<101::AID-HON629>3.0.CO;2-#"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2010.491137"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026454831340"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm090"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428190109097649"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-10-671826"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.38.0410"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-595801"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090331"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-282780"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1942"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411087"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510665"},{"key":"e_1_2_9_37_1","doi-asserted-by":"crossref","unstructured":"LesokhinAM AnsellSM ArmandP et al.Preliminary Results of a Phase I Study of Nivolumab (BMS\u2010936558) in Patients with Relapsed or Refractory Lymphoid Malignancies.Blood2014; [abstract 291 American Society of Hematology Meeting].","DOI":"10.1182\/blood.V124.21.291.291"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-567453"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","unstructured":"ZinzaniPL RibragV MoskowitzCH et al.Phase 1b Study of PD\u20101 Blockade with Pembrolizumab in Patients with Relapsed\/Refractory Primary Mediastinal Large B\u2010Cell Lymphoma (PMBCL).Blood2015; [abstract 3986 American Society of Hematology Meeting].","DOI":"10.1182\/blood.V126.23.3986.3986"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305133"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507643"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503093"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501824"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412082"},{"key":"e_1_2_9_46_1","doi-asserted-by":"crossref","unstructured":"AnsellSM ArmandP TimmermanJ et al.Nivolumab in Patients (Pts) with Relapsed or Refractory Classical Hodgkin Lymphoma (R\/R cHL): Clinical Outcomes from Extended Follow\u2010up of a Phase 1 Study (CA209\u2010039).Blood2015; [abstract 583 American Society of Hematology Meeting].","DOI":"10.1182\/blood.V126.23.583.583"},{"key":"e_1_2_9_47_1","doi-asserted-by":"crossref","unstructured":"HerbauxC GauthierJ BriceP et al.Nivolumab Is Effective and Reasonably Safe in Relapsed or Refractory Hodgkin's Lymphoma after Allogeneic Hematopoietic Cell Transplantation: A Study from the Lysa and SFGM\u2010TC.Blood2015; [abstract 3979 American Society of Hematology Meeting].","DOI":"10.1182\/blood.V126.23.3979.3979"},{"key":"e_1_2_9_48_1","doi-asserted-by":"crossref","unstructured":"MoskowitzCH RibragV MichotJ\u2010M et al.PD\u20101 Blockade with the Monoclonal Antibody Pembrolizumab (MK\u20103475) in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Preliminary Results from a Phase 1b Study (KEYNOTE\u2010013).Blood2014; [abstract 290 American Society of Hematology Meeting].","DOI":"10.1182\/blood.V124.21.290.290"},{"key":"e_1_2_9_49_1","doi-asserted-by":"crossref","unstructured":"ArmandP ShippMA RibragV et al.PD\u20101 Blockade with Pembrolizumab in Patients with Classical HodgkinLymphoma after Brentuximab Vedotin Failure: Safety Efficacy and Biomarker Assessment.Blood2015; [abstract 584 American Society of Hematology Meeting].","DOI":"10.1182\/blood.V126.23.584.584"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13920"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.346"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200690"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200694"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.21.9543-9553.2005"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192461099"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3025"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.05.016"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090847"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.32.8401"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3129"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.02.018"},{"key":"e_1_2_9_63_1","unstructured":"Oncologist 2016 21 PD\u20101 immune checkpoint inhibitors show promising activity in relapsed\/refractory Hodgkin lymphoma"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70455-3"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-014-1698-z"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2011.594926"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004594107"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-507947"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1505857"},{"key":"e_1_2_9_70_1","author":"Merryman R","year":"2015","journal-title":"Blood"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.03.021"},{"key":"e_1_2_9_72_1","doi-asserted-by":"crossref","unstructured":"WangH ChengF ChengJ et al.JQ1 a Selective Bromodomain Inhibitor Augment the Immunogenicity of Mantle Cell Lymphoma By Influencing the Expression of PD\u2010L1.Blood2015; [abstract 822 American Society of Hematology Meeting].","DOI":"10.1182\/blood.V126.23.822.822"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.355"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2014.58"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejh.12770","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.12770","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:04:41Z","timestamp":1696291481000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.12770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,30]]},"references-count":73,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1111\/ejh.12770"],"URL":"https:\/\/doi.org\/10.1111\/ejh.12770","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"value":"0902-4441","type":"print"},{"value":"1600-0609","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,30]]}}}