{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T23:28:54Z","timestamp":1764458934885,"version":"3.40.5"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","award":["20159848"],"award-info":[{"award-number":["20159848"]}],"id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C9203\/A17750"],"award-info":[{"award-number":["C9203\/A17750"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Proteasome inhibitors have been associated with thrombotic microangiopathy (TMA) \u2014 a group of disorders characterised by occlusive microvascular thrombosis causing microangiopathic haemolytic anaemia, thrombocytopenia and end\u2010organ damage. To date, carfilzomib\u2010associated TMA has predominantly been described in relapsed\/refractory myeloma patients. We report eight patients with newly diagnosed myeloma who experienced TMA events while receiving carfilzomib on the phase II CARDAMON trial. The first three occurred during maintenance single\u2010agent carfilzomib, two occurred at induction with carfilzomib given with cyclophosphamide and dexamethasone (KCd) and three occurred during KCd consolidation. At TMA presentation 6\/8 were hypertensive; 7\/8 had acute kidney injury and in three, renal impairment persisted after resolution of TMA in other respects. The mechanism of carfilzomib\u2010associated TMA remains unclear, though patients with known hypertension seem particularly susceptible. Given the first three cases occurred during maintenance after a longer than five\u2010week treatment break, a protocol amendment was instituted with: aggressive hypertension management, carfilzomib step\u2010up dosing (20\u00a0mg\/m<jats:sup>2<\/jats:sup> on day 1) at start of maintenance before dose escalation to 56\u00a0mg\/m<jats:sup>2<\/jats:sup> maximum, and adding 10\u00a0mg dexamethasone as premedication to maintenance carfilzomib infusions. No further TMA events occurred during maintenance following this amendment and the TMA incidence reduced from 4\u00b72 to 1\u00b76 per 1\u00a0000 patient cycles.<\/jats:p>","DOI":"10.1111\/bjh.17377","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T07:33:47Z","timestamp":1614670427000},"page":"750-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Thrombotic microangiopathy in untreated myeloma patients receiving carfilzomib, cyclophosphamide and dexamethasone on the CARDAMON study"],"prefix":"10.1111","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4161-8275","authenticated-orcid":false,"given":"Marquita","family":"Camilleri","sequence":"first","affiliation":[{"name":"Haematology Department University College Hospitals London UK"},{"name":"Cancer Institute University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Cuadrado","sequence":"additional","affiliation":[{"name":"Haematology Department University College Hospitals London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Phillips","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences University of Manchester Manchester Cancer Research Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Wilson","sequence":"additional","affiliation":[{"name":"Cancer Research UK and UCL Cancer Trials Centre University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Jenner","sequence":"additional","affiliation":[{"name":"Cancer Research UK and UCL Cancer Trials Centre University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Pang","sequence":"additional","affiliation":[{"name":"Cancer Research UK and UCL Cancer Trials Centre University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumaiya","family":"Kamora","sequence":"additional","affiliation":[{"name":"Cancer Research UK and UCL Cancer Trials Centre University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Streetly","sequence":"additional","affiliation":[{"name":"Haematology Department Guys and St Thomas\u2019 NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6553-4618","authenticated-orcid":false,"given":"Rakesh","family":"Popat","sequence":"additional","affiliation":[{"name":"Haematology Department University College Hospitals London UK"},{"name":"Cancer Institute University College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1571-0692","authenticated-orcid":false,"given":"Ceri","family":"Bygrave","sequence":"additional","affiliation":[{"name":"University Hospital of Wales Cardiff UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Owen","sequence":"additional","affiliation":[{"name":"HMDS Laboratory St James\u2019 Institute of Oncology Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Cavenagh","sequence":"additional","affiliation":[{"name":"Haematology Department Barts Health NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Chapman","sequence":"additional","affiliation":[{"name":"Haematology Department Cambridge Institute for Medical Research Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1393-2793","authenticated-orcid":false,"given":"Jonathan","family":"Sive","sequence":"additional","affiliation":[{"name":"Haematology Department University College Hospitals London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Eccersley","sequence":"additional","affiliation":[{"name":"Haematology Department Barts Health NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Sheaff","sequence":"additional","affiliation":[{"name":"Cellular Pathology Department Barts Health NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reuben","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Haematology Department Kings College Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthik","family":"Ramasamy","sequence":"additional","affiliation":[{"name":"Haematology Department Oxford University Hospitals NHS Trust Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-0412","authenticated-orcid":false,"given":"Gordon","family":"Cook","sequence":"additional","affiliation":[{"name":"Leeds Institute of Clinical Trial Research University of Leeds Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres","family":"Virchis","sequence":"additional","affiliation":[{"name":"Haematology Department Royal Free Hospitals NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-9847","authenticated-orcid":false,"given":"Selina J.","family":"Chavda","sequence":"additional","affiliation":[{"name":"Haematology Department University College Hospitals London UK"},{"name":"Haematology Department Guys and St Thomas\u2019 NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Clifton\u2010Hadley","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences University of Manchester Manchester Cancer Research Centre Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2443-6517","authenticated-orcid":false,"given":"Marie Anne","family":"Scully","sequence":"additional","affiliation":[{"name":"Haematology Department University College Hospitals London UK"},{"name":"Cardiometabolic Programme NIHR UCLH\/UCL Biomedical Research Centre London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-276X","authenticated-orcid":false,"given":"Kwee","family":"Yong","sequence":"additional","affiliation":[{"name":"Haematology Department University College Hospitals London UK"},{"name":"Haematology Department Guys and St Thomas\u2019 NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1312353"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-743104"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2019.106195"},{"issue":"2","key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.4081\/hr.2012.e13","article-title":"Thrombotic microangiopathy associated with bortezomib treatment in a patient with relapsed multiple myeloma","volume":"4","author":"Salmenniemi U","year":"2012","journal-title":"Hematol Rep"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-008-0140-1"},{"key":"e_1_2_7_7_1","first-page":"6020691","article-title":"Renal thrombotic microangiopathy associated with the use of bortezomib in a patient with multiple myeloma","volume":"2016","author":"Van Keer J","year":"2016","journal-title":"Case Rep Hematol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2014.977887"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25832"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2014.02.005"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00464-7"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2016.62"},{"volume-title":"Kyprolis\u00ae (carfilzomib) for injection, for intravenous use [package insert]","key":"e_1_2_7_13_1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2016.03.002"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V120.21.5037.5037"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-15-156"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfv059"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-556308"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jca.21371"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24447"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.12691\/ajmcr-7-10-5"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2019.09.449"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018027532"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2020.01.016"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16796"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.112"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.327"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-563759"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2011.07.028"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1195"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.17377","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.17377","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.17377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:37:19Z","timestamp":1693298239000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.17377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1111\/bjh.17377"],"URL":"https:\/\/doi.org\/10.1111\/bjh.17377","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"type":"print","value":"0007-1048"},{"type":"electronic","value":"1365-2141"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"2020-12-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}