{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:38:52Z","timestamp":1790231932853,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T00:00:00Z","timestamp":1408406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Dickkopf\u20101 (<jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. <jats:styled-content style=\"fixed-case\">BHQ<\/jats:styled-content>880, a human neutralizing IgG1 anti\u2010<jats:styled-content style=\"fixed-case\">DKK<\/jats:styled-content>1 monoclonal antibody, is being investigated for its impact on multiple myeloma\u2010related bone disease and as an agent with potential anti\u2010myeloma activity. The primary objectives of this Phase <jats:styled-content style=\"fixed-case\">IB<\/jats:styled-content> study were to determine the maximum tolerated dose (<jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content>) of <jats:styled-content style=\"fixed-case\">BHQ<\/jats:styled-content>880 and to characterize the dose\u2010limiting toxicity (<jats:styled-content style=\"fixed-case\">DLT<\/jats:styled-content>) of escalating doses in combination with anti\u2010myeloma therapy and zoledronic acid. Twenty\u2010eight patients were enrolled and received <jats:styled-content style=\"fixed-case\">BHQ<\/jats:styled-content>880 at doses of 3\u201340\u00a0mg\/kg. No <jats:styled-content style=\"fixed-case\">DLT<\/jats:styled-content>s were reported, therefore, the <jats:styled-content style=\"fixed-case\">MTD<\/jats:styled-content> was not determined. The recommended Phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> dose was declared as 10\u00a0mg\/kg, based mainly on saturation data. There was a general trend towards increased bone mineral density (<jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>) observed over time; specific increases in spine <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content> from Cycle 12 onwards irrespective of new skeletal\u2010related events on study were observed, and increases in bone strength at the spine and hip were also demonstrated in some patients. <jats:styled-content style=\"fixed-case\">BHQ<\/jats:styled-content>880 in combination with zoledronic acid and anti\u2010myeloma therapy was well tolerated and demonstrated potential clinical activity in patients with relapsed or refractory multiple myeloma.<\/jats:p>","DOI":"10.1111\/bjh.13056","type":"journal-article","created":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T10:36:52Z","timestamp":1408444612000},"page":"366-375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":151,"title":["A Phase <scp>IB<\/scp> multicentre dose\u2010determination study of <scp>BHQ<\/scp>880 in combination with anti\u2010myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal\u2010related events"],"prefix":"10.1111","volume":"167","author":[{"given":"Swaminathan P.","family":"Iyer","sequence":"first","affiliation":[{"name":"Houston Methodist Cancer Center Weill Cornell Medical College Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph Taddeus","family":"Beck","sequence":"additional","affiliation":[{"name":"Highlands Oncology Group P.A. Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Keith","family":"Stewart","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Mayo Clinic College of Medicine Scottsdale AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatin","family":"Shah","sequence":"additional","affiliation":[{"name":"Lymphoma and Myeloma University of Texas M.D. Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R.","family":"Kelly","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanela","family":"Bilic","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Sen","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil C.","family":"Munshi","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute and Boston VA Healthcare System Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2005.03.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010401)91:7<1191::AID-CNCR1119>3.0.CO;2-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa013444"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.3.482"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.03.016"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.thj.6200312"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-191577"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728214.2012.713345"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.02.017"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00571-2"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.5.966"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.081104"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2008.01164.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2008.01065.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01372.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.03.017"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21342"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70157-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.060311"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00041-7"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.173"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22033"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.01.012"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-132134"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-120253"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.08009.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21913"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11701"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02883"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20774"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.235"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030847"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-047712"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2011.41"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.13056","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.13056","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.13056","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.13056","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:11:20Z","timestamp":1696317080000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.13056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,19]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1111\/bjh.13056"],"URL":"https:\/\/doi.org\/10.1111\/bjh.13056","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,19]]},"assertion":[{"value":"2014-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-05-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}