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MM was triple-class refractory in 38% of patients and 53% of patients had high-risk cytogenetics del(17p), t(4;14), t(14;16) and\/or gain 1q. Common treatment-related adverse events (all\/Grade 3) were thrombocytopenia 72%\/47% (G3 and G4), nausea 72%\/6%, anaemia 53%\/19% and fatigue 53%\/9%, all expected and manageable with supportive care and dose modifications. MTD and RP2D were identified as selinexor 80\u2009mg, carfilzomib 56\u2009mg\/m<jats:sup>2<\/jats:sup>, and dexamethasone 40\u2009mg, all QW. The overall response rate was 78% including 14 (44%)\u2009\u2265\u2009very good partial responses. Median progression-free survival was 15 months.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Weekly XKd is highly effective and well-tolerated. These data support further investigation of XKd in patients with MM.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41416-021-01608-2","type":"journal-article","created":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T19:02:29Z","timestamp":1637434949000},"page":"718-725","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients"],"prefix":"10.1038","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-5605","authenticated-orcid":false,"given":"Cristina","family":"Gasparetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Schiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha A.","family":"Tuchman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie S.","family":"Callander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhamed","family":"Baljevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Lentzsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana C.","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Kotb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nizar J.","family":"Bahlis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine I.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Sutherland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Madan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"LeBlanc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sebag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Venner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William I.","family":"Bensinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Biran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Ammu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osnat","family":"Ben-Shahar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"DeCastro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Van Domelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad S.","family":"Bentur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatin","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Shacham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kauffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brea","family":"Lipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,20]]},"reference":[{"key":"1608_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/leu.2013.115","volume":"28","author":"YT Tai","year":"2014","unstructured":"Tai YT, Landesman Y, Acharya C, Calle Y, Zhong MY, Cea M. et al. 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EHA. 2021;abstract S188.","DOI":"10.1038\/s41416-021-01608-2"}],"container-title":["British Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41416-021-01608-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-021-01608-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-021-01608-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:04:20Z","timestamp":1646179460000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41416-021-01608-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,20]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,3,23]]}},"alternative-id":["1608"],"URL":"https:\/\/doi.org\/10.1038\/s41416-021-01608-2","relation":{},"ISSN":["0007-0920","1532-1827"],"issn-type":[{"value":"0007-0920","type":"print"},{"value":"1532-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,20]]},"assertion":[{"value":"14 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"CG\u2014advisory board: Karyopharm, Abbvie, Janssen, GSK, Sanofi, Oncopeptide; speaker: Karyopharm, GSK, Sanofi. GJS\u2014research funding from Karyopharm. SAT\u2014honoraria\/advisory board: Karyopharm, Caelum, Sanofi; research funding: Karyopharm, Sanofi, Caelum; consultancy: Oncopeptides. NSC\u2014nothing to disclose. MB\u2014Independent Review Committee member and consultant: Karyopharm; advisory role and consultant: BMS\/Celgene; advisory role: Oncopeptides, Johnson & Johnson; research support: Amgen, Exelixis. SL\u2014consultant advisory role: Caelum Bioscience, Sorrento, Janssen, Celularity, Abbvie, GSK, Takeda, Karyopharm, Sanofi, Oncopetide; stock ownership: Caelum Bioscience, Magenta; research grant: Karyopharm, Sanofi. ACR\u2014consultant: BMS, Celgene, Amgen, Janssen; research support: BMS, Karyopharm, Abbvie. RK\u2014research funding: Merck, Sanofi; patents, royalties, other intellectual property: none; stock and other ownership interests: Karyopharm; consulting or advisory role: Celgene\/BMS; Janssen; Amgen; Takeda; Sanofi; Merck; honoraria: none; speakers\u2019 bureau: none; travel, accommodations, expenses: none. DW\u2014honoraria: Amgen, Antengene, Celgene\/BMS, GSK, Janssen, Karyopharm, Sanofi, Takeda. NJB\u2014honoraria: Janssen, Celgene, Amgen, Takeda, AbbVie, GlaxoSmithKline, Sanofi, Genentech and Karyopharm; consultant\/advisor role: Janssen, Celgene, Amgen, Takeda, AbbVie, GlaxoSmithKline, Karyopharm and Genentech. CIC\u2014research funding: Gilead, BMS; consultant or advisory: BMS, Novartis, Gilead, Abbvie, Beigene. HJS\u2014honoraria and consultant or advisory role: Amgen, Takeda, Celgene, BMS, Janssen, Sanofi-Genzyme. SM\u2014consultant or advisory role: ad hoc advisory board for BMS, Takeda, Sanofi, Janssen, Amgen; GSK; speakers\u2019 bureau: BMS, GSK, Takeda, Janssen, Karyopharm. RL\u2014research funding: BMS\/Celgene; consultant or advisory role: Janssen, BMS\/Celgene, Amgen, Sanofi, Takeda. MS\u2014advisory boards: Janssen, Karyopharm, Amgen, Novartis, Bristol-Myers Squibb, Takeda; no other disclosures. CPV\u2014honoraria from BMS\/Celgene, Janssen, Sanofi, GSK, Takeda. WIB\u2014research funding: BMS, Karyopharm, Poseida, Harpoon, Regeneron, Janssen, Sanofi; consulting: Janssen, Regeneron, BMS; honoraria\/speakers\u2019 bureau: Takeda, BMS, Amgen, Janssen; no travel in the past year. NB\u2014consultant: Karyopharm, BMS\/Celgene, Sanofi, Janssen, Oncopeptides; research support: Karyopharm, BMS\/Celgene, Janssen, Merck; speakers\u2019 bureau: Oncopeptides, Janssen; advisory board: BMS\/Celgene, Sanofi. SA\u2014employee and stock holder in Karyopharm Therapeutics. OB-S\u2014employee and stockholder in Karyopharm Therapeutics. AD\u2014employee and stockholder in Karyopharm Therapeutics. DVD\u2014employee and stockholder in Karyopharm Therapeutics. TZ\u2014a former employee and stockholder in Karyopharm Therapeutics. CZ\u2014employee and stockholder in Karyopharm Therapeutics. OSB\u2014employee and stockholder in Karyopharm Therapeutics. JS\u2014CMO, employee and stockholder in Karyopharm Therapeutics. SS\u2014President, employee and stockholder in Karyopharm Therapeutics; patents and royalties: (8999996, 9079865, 9714226, PCT\/US12\/048319, and I574957) on hydrazide-containing nuclear transport modulators and uses, and pending patents (PCT\/US12\/048319, 499\/2012, PI20102724, and 2012000928). MGK\u2014CEO, employee and stockholder in Karyopharm Therapeutics. BL\u2014advisory role: BMS, GSK, Janssen, Karyopharm.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study protocol was approved by the institutional review board or an independent ethics committee at each participating centre and was in accordance with the Declaration of Helsinki, the International Conference on Harmonisation-Good Clinical Practice and local laws. All patients provided written informed consent prior to enrollment.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}