{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T05:16:45Z","timestamp":1770441405762,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T00:00:00Z","timestamp":1423785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007072","name":"Onyx Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007072","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Sixty\u2010four transplant\u2010eligible patients with newly diagnosed multiple myeloma (<jats:styled-content style=\"fixed-case\">NDMM<\/jats:styled-content>) received carfilzomib (days 1, 2, 8, 9, 15, 16), 300\u00a0mg\/m<jats:sup>2<\/jats:sup> cyclophosphamide (days 1, 8, 15), 100\u00a0mg thalidomide (days 1\u201328) and 40\u00a0mg dexamethasone (days 1, 8, 15, 22) in 28\u2010day cycles (<jats:styled-content style=\"fixed-case\">CYKLONE<\/jats:styled-content> regimen). Carfilzomib was dose\u2010escalated to 15\/20, 20\/27, 20\/36 and 20\/45\u00a0mg\/m<jats:sup>2<\/jats:sup> to determine the maximum tolerated dose (<jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>), which was 20\/36\u00a0mg\/m<jats:sup>2<\/jats:sup>. Regardless of attribution, common Grade 3 or higher adverse events were lymphopenia (38%), neutropenia (23%) and anaemia (20%). All peripheral neuropathy (31%) was Grade 1 and considered most likely to be thalidomide\u2010related. Common cardiac or pulmonary events of any grade in \u22655% of patients included dyspnoea (20%) and cough (6%). Overall (<jats:italic>N<\/jats:italic>\u00a0=\u00a064), 91% of patients achieved a best response of partial response or better across all cycles of treatment, including five patients with complete responses. At the <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0=\u00a029), 59% of patients achieved a very good partial response or better after four cycles (primary end point). Stem cell collection was successful in all patients in whom it was attempted (<jats:italic>n<\/jats:italic>\u00a0=\u00a042). Progression\u2010free survival and overall survival at 24\u00a0months was 76% and 96%, respectively (median follow\u2010up of 17\u00b75\u00a0months). <jats:styled-content style=\"fixed-case\">CYKLONE<\/jats:styled-content> appears highly efficacious in <jats:styled-content style=\"fixed-case\">NDMM<\/jats:styled-content> patients, with manageable toxicities.<\/jats:p>","DOI":"10.1111\/bjh.13296","type":"journal-article","created":{"date-parts":[[2015,2,14]],"date-time":"2015-02-14T05:05:38Z","timestamp":1423890338000},"page":"219-227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Phase Ib\/II trial of <scp>CYKLONE<\/scp> (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma"],"prefix":"10.1111","volume":"169","author":[{"given":"Joseph R.","family":"Mikhael","sequence":"first","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig B.","family":"Reeder","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward N.","family":"Libby","sequence":"additional","affiliation":[{"name":"University of Washington\/Fred Hutchinson Cancer Research Center Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano J.","family":"Costa","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Charleston SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Leif","family":"Bergsagel","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Buadi","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester MN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Mayo","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sravan K.","family":"Nagi Reddy","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Gano","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amylou C.","family":"Dueck","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Keith","family":"Stewart","sequence":"additional","affiliation":[{"name":"Mayo Clinic Scottsdale AZ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,2,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00930.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0522"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61424-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4086"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-422683"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08949.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1182\/blood.V122.21.538.538","article-title":"Phase II clinical and correlative study of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide extended dosing (CRD\u2010R) induces high rates of MRD negativity in newly diagnosed multiple myeloma (MM) patients","volume":"122","author":"Korde N.","year":"2013","journal-title":"Blood"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-065888"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2009.0603"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-395749"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.291"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2013.01.019"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-117457"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.52.0023"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.52.3522"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.02.116"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.0221"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.1853"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1182\/blood.V118.21.1872.1872","article-title":"Bortezomib, lenalidomide, and dexamethasone (VRD) consolidation and lenalidomide maintenance in frontline multiple myeloma patients: updated results of the IFM 2008 phase II VRD intensive program","volume":"118","author":"Roussel M.","year":"2011","journal-title":"Blood"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1182\/blood.V122.21.690.690","article-title":"Phase I\/II dose expansion of a multi\u2010center trial of carfilzomib and pomalidomide with dexamethasone (Car\u2010Pom\u2010d) in patients with relapsed\/refractory multiple myeloma","volume":"122","author":"Shah J.J.","year":"2013","journal-title":"Blood"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1182\/blood.V122.21.688.688","article-title":"Dose escalation phase 2 trial of carfilzomib combined with thalidomide and low\u2010dose dexamethasone in newly diagnosed, transplant eligible patients with multiple myeloma. 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