{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:41:55Z","timestamp":1790876515050,"version":"4.1.0"},"reference-count":126,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tagraxofusp is a first\u2010in\u2010class CD123\u2010directed conjugate of an amended diphtheria toxin platform and recombinant interleukin 3. Binding and subsequent internalization of the drug result in cell death via disruption of intracellular protein synthesis. CD123 is a surface marker that is expressed in several hematological malignancies, especially blastic plasmacytoid dendritic cell neoplasm (BPDCN), where its expression is ubiquitous. A pivotal study of tagraxofusp in BPDCN resulted in its approval for the treatment of BPDCN, the first treatment approved for this indication. Since the introduction of tagraxofusp, research has focused on the management of adverse effects, combination therapy to improve outcomes in fit patients, and dosing and combination strategies to mitigate toxicities while preserving efficacy, especially among older patients. The successful targeting of CD123 in BPDCN has also encouraged research into a variety of other CD123\u2010positive hematological neoplasms, including acute myeloid leukemia (AML), and informed the development of other novel agents targeting CD123. This review examines the clinical data leading to the development and approval of tagraxofusp in BPDCN, how it is being used in combination to improve outcomes in BPDCN and AML, and its developing role in other hematological malignancies.<\/jats:p>","DOI":"10.1002\/cncr.35315","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T13:34:21Z","timestamp":1713188061000},"page":"2260-2271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tagraxofusp, a first\u2010in\u2010class CD123\u2010targeted agent: Five\u2010year postapproval comprehensive review of the literature"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-3362","authenticated-orcid":false,"given":"Wei\u2010Ying","family":"Jen","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-2212","authenticated-orcid":false,"given":"Marina","family":"Konopleva","sequence":"additional","affiliation":[{"name":"Department of Oncology Montefiore Einstein Comprehensive Cancer Center  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1670-6513","authenticated-orcid":false,"given":"Naveen","family":"Pemmaraju","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"issue":"6","key":"e_1_2_15_2_1","first-page":"1730","article-title":"A diphtheria toxin\u2010interleukin 3 fusion protein is cytotoxic to primitive acute myeloid leukemia progenitors but spares normal progenitors","volume":"62","author":"Feuring\u2010Buske M","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(78)90099\u20105"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0021\u20109258(19)52509\u20101"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0021\u20109258(18)93347\u20108"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/13.8.575"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1996.1"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci113727"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201003\u2010079681"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102001\u201011\u20100097"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401903"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2020.01.005"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201006\u2010578633"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.4789.4789"},{"key":"e_1_2_15_15_1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow S","year":"2008"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102016\u201003\u2010643544"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010022\u201001613\u20101"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.072645"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010191150"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1556"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdh268"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10489"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181c5e26b"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102022\u2010170956"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7101"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.e19043"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.3812.381"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006645"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001144"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001875"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011308"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010021\u201001478\u20105"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102015\u201001\u2010621268"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.12.706"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010181031"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010022\u201000806\u20100"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13184680"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596\u2010021\u20102393\u20103"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003359"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v97.10.3210"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/pas.0000000000001316"},{"issue":"21","key":"e_1_2_15_42_1","article-title":"Preclinical studies of SL\u2010401, a targeted therapy directed to the interleukin\u20103 receptor (IL3\u2010R), in blastic plasmacytoid dendritic cell neoplasm (BPDCN): potent activity in BPDCN cell lines, primary tumor, and in an in vivo model","volume":"122","author":"Fanny D","year":"2013","journal-title":"Blood"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.188193"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2003.11.005"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc980015a"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201004\u2010566737"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1815105"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201019\u20102329"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010018\u20100604\u20106"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.00034"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.Hs9.0000845012.43915.11"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010178734"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011586"},{"key":"e_1_2_15_54_1","unstructured":"National Institute for Health and Care Excellence.Tagraxofusp for Treating Blastic Plasmacytoid Dendritic Cell Neoplasm (Terminated Appraisal). Accessed December 31 2023.https:\/\/www.nice.org.uk\/guidance\/ta782"},{"key":"e_1_2_15_55_1","unstructured":"Menarini Group.Japanese Ministry of Health Labor and Welfare Grants Orphan Drug Designation to Tagraxofusp for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). Accessed December 31 2023.https:\/\/www.menarini.com\/en\u2010us\/news\/news\u2010detail\/the\u2010menarini\u2010group\u2010announces\u2010elzonris174\u2010tagraxofusp\u2010designated\u2010as\u2010an\u2010orphan\u2010drug\u2010for\u2010bpdcn\u2010by\u2010japanese\u2010ministry\u2010of\u2010health\u2010labor\u2010and\u2010welfare"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102020\u2010137207"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010178874"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1177\/2048872612455142"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2021.09.009"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2020.1701651"},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000173"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010019\u20100184\u20106"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2016.09.003"},{"key":"e_1_2_15_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010018\u20100265\u2010z"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci128571"},{"key":"e_1_2_15_66_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci132443"},{"key":"e_1_2_15_67_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.Cd\u201016\u20100999"},{"key":"e_1_2_15_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26417"},{"key":"e_1_2_15_69_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102021\u2010147486"},{"key":"e_1_2_15_70_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010180010"},{"key":"e_1_2_15_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2021.02.008"},{"key":"e_1_2_15_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011817"},{"key":"e_1_2_15_73_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280843"},{"key":"e_1_2_15_74_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102022\u2010158985"},{"key":"e_1_2_15_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403224"},{"key":"e_1_2_15_76_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102002\u201003\u20100852"},{"issue":"12","key":"e_1_2_15_77_1","first-page":"1261","article-title":"Interleukin\u20103 receptor alpha chain (CD123) is widely expressed in hematologic malignancies","volume":"86","author":"Mu\u00f1oz L","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_15_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185\u2010014\u20101590\u20102"},{"key":"e_1_2_15_79_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci67580"},{"key":"e_1_2_15_80_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201007\u2010099226"},{"key":"e_1_2_15_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010019\u20100447\u20103"},{"key":"e_1_2_15_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800707"},{"key":"e_1_2_15_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12477"},{"key":"e_1_2_15_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.5577.5577"},{"key":"e_1_2_15_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hemonc.2019.01.001"},{"key":"e_1_2_15_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.135"},{"key":"e_1_2_15_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.08.019"},{"key":"e_1_2_15_88_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v100.1.230"},{"key":"e_1_2_15_89_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.3234"},{"key":"e_1_2_15_90_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701799035"},{"key":"e_1_2_15_91_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.31.15_suppl.7029"},{"key":"e_1_2_15_92_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010189417"},{"key":"e_1_2_15_93_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2012971"},{"key":"e_1_2_15_94_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011721"},{"key":"e_1_2_15_95_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102022\u2010170738"},{"key":"e_1_2_15_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2152\u20102650(22)01287\u20103"},{"key":"e_1_2_15_97_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.7059"},{"key":"e_1_2_15_98_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102021\u2010147827"},{"key":"e_1_2_15_99_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102019\u2010131217"},{"key":"e_1_2_15_100_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102021\u2010145276"},{"key":"e_1_2_15_101_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102022\u2010163503"},{"key":"e_1_2_15_102_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007897"},{"key":"e_1_2_15_103_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201099\u2010119081"},{"key":"e_1_2_15_104_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.253740"},{"key":"e_1_2_15_105_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143545"},{"key":"e_1_2_15_106_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143375"},{"key":"e_1_2_15_107_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010186126"},{"key":"e_1_2_15_108_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008745"},{"key":"e_1_2_15_109_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000967468.85099.f4"},{"key":"e_1_2_15_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(23)00674\u20105"},{"key":"e_1_2_15_111_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010173413"},{"key":"e_1_2_15_112_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V130.Suppl_1.811.811"},{"key":"e_1_2_15_113_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007732"},{"key":"e_1_2_15_114_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010956"},{"key":"e_1_2_15_115_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010190693"},{"key":"e_1_2_15_116_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102022\u2010167468"},{"key":"e_1_2_15_117_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010173162"},{"key":"e_1_2_15_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201029669\u20108"},{"key":"e_1_2_15_119_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2022.106928"},{"key":"e_1_2_15_120_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017865"},{"key":"e_1_2_15_121_1","doi-asserted-by":"publisher","DOI":"10.1097\/hs9.0000000000000841"},{"key":"e_1_2_15_122_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010188546"},{"key":"e_1_2_15_123_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13235888"},{"key":"e_1_2_15_124_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010019\u20100262\u20100"},{"key":"e_1_2_15_125_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007879"},{"key":"e_1_2_15_126_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010021\u201001228\u2010y"},{"key":"e_1_2_15_127_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102020\u2010137665"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.35315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T14:54:09Z","timestamp":1760280849000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.35315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,15]]},"references-count":126,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/cncr.35315"],"URL":"https:\/\/doi.org\/10.1002\/cncr.35315","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,15]]},"assertion":[{"value":"2024-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}