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This phase 1\/2 study (<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>01383928) evaluated the recommended phase 2 dose (<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>2D), pharmacokinetics, safety and efficacy of twice\u2010weekly ixazomib plus Rd in <jats:styled-content style=\"fixed-case\">NDMM<\/jats:styled-content>; 64 patients were enrolled across both phases. Patients received twice\u2010weekly oral ixazomib 3\u00b70 or 3\u00b77\u00a0mg plus lenalidomide 25\u00a0mg and dexamethasone 20\u00a0mg (10\u00a0mg in cycles 9\u201316) for up to sixteen 21\u2010day cycles, followed by maintenance with twice\u2010weekly ixazomib alone. No dose\u2010limiting toxicities were reported in cycle 1; the <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>2D was 3\u00b70\u00a0mg based on overall tolerability across multiple cycles. In 62 evaluable patients, the confirmed overall response rate was 94% (68% \u2265very good partial response; 24% complete response). Median progression\u2010free survival was 24\u00b79\u00a0months. Responses (median duration 36\u00b79\u00a0months for patients receiving the <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>2D) deepened during treatment. Grade 3 drug\u2010related adverse events (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s) occurred in 64% of patients, including: rash, 13%; peripheral neuropathy, 8%; hyperglycaemia, 8%. There were no grade 4 drug\u2010related <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s. Thirteen patients discontinued due to <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s. Twice\u2010weekly ixazomib\u2010Rd offers substantial activity with promising long\u2010term outcomes in <jats:styled-content style=\"fixed-case\">NDMM<\/jats:styled-content> patients but may be associated with greater toxicity compared with weekly ixazomib\u2010Rd in this setting.<\/jats:p>","DOI":"10.1111\/bjh.15394","type":"journal-article","created":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T11:26:29Z","timestamp":1529925989000},"page":"231-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Twice\u2010weekly ixazomib in combination with lenalidomide\u2010dexamethasone in patients with newly diagnosed multiple myeloma"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-8865","authenticated-orcid":false,"given":"Paul G.","family":"Richardson","sequence":"first","affiliation":[{"name":"Dana\u2010Farber Cancer Institute Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig C.","family":"Hofmeister","sequence":"additional","affiliation":[{"name":"Ohio State University Columbus OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara A.","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology University of Chicago Medicine Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myo","family":"Htut","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplant City of Hope National Medical Center Duarte Duarte CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Vesole","sequence":"additional","affiliation":[{"name":"John Theurer Cancer Center Hackensack University Medical Center Hackensack NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus G.","family":"Berdeja","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8945-5850","authenticated-orcid":false,"given":"Michaela","family":"Liedtke","sequence":"additional","affiliation":[{"name":"Stanford Comprehensive Cancer Center Stanford CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajai","family":"Chari","sequence":"additional","affiliation":[{"name":"Mount Sinai School of Medicine Ruttenberg Treatment Center New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Lebovic","sequence":"additional","affiliation":[{"name":"University of Michigan Cancer Center Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noopur","family":"Raje","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catriona","family":"Byrne","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals Inc. 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