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Non\u2010clinical studies support combining selinexor with proteasome inhibitors (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>s) and corticosteroids to overcome resistance in relapsed\/refractory multiple myeloma (<jats:styled-content style=\"fixed-case\">RRMM<\/jats:styled-content>). We conducted a phase I dose\u2010escalation trial of twice\u2010weekly selinexor in combination with carfilzomib and dexamethasone (<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>d) to determine maximum tolerated dose in patients with <jats:styled-content style=\"fixed-case\">RRMM<\/jats:styled-content> (<jats:italic>N<\/jats:italic>\u00a0=\u00a021), with an expansion cohort to assess activity in carfilzomib\u2010refractory disease and identify a recommended phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> dose (<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>2D). During dose escalation, there was one dose\u2010limiting toxicity (cardiac failure). The <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>2D of twice\u2010weekly <jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>d was selinexor 60\u00a0mg, carfilzomib 20\/27\u00a0mg\/m<jats:sup>2<\/jats:sup> and dexamethasone 20\u00a0mg. The most common grade 3\/4 treatment\u2010emergent adverse events included thrombocytopenia (71%), anaemia (33%), lymphopenia (33%), neutropenia (33%) and infections (24%). Rates of \u2265minimal response, \u2265partial response and very good partial response were 71%, 48% and 14%, respectively; similar response outcomes were observed for dual\u2010class refractory (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content> and immunomodulatory drug)\/quad\u2010exposed (carfilzomib, bortezomib, lenalidomide and pomalidomide) patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a017), and patients refractory to carfilzomib in last line of therapy (<jats:italic>n<\/jats:italic>\u00a0=\u00a013). Median progression\u2010free survival was 3\u00b77\u00a0months, and overall survival was 22\u00b74\u00a0months in the overall population. <jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>d was tolerable and re\u2010established disease control in <jats:styled-content style=\"fixed-case\">RRMM<\/jats:styled-content> patients, including carfilzomib\u2010refractory patients.<\/jats:p><jats:p>Registered at ClinicalTrials.gov (NCT02199665)<\/jats:p>","DOI":"10.1111\/bjh.15969","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T10:09:16Z","timestamp":1558692556000},"page":"549-560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed\/refractory multiple myeloma"],"prefix":"10.1111","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4550-4726","authenticated-orcid":false,"given":"Andrzej J.","family":"Jakubowiak","sequence":"first","affiliation":[{"name":"University of Chicago Medical Center Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jagoda K.","family":"Jasielec","sequence":"additional","affiliation":[{"name":"University of Chicago Medical Center Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3576-9106","authenticated-orcid":false,"given":"Cara A.","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig E.","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Hematology\/Oncology University of Michigan School of Medicine Ann Arbor MI 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