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We evaluated the safety and efficacy of Ven and dexamethasone (VenDex) combination in patients with t(11;14) positive relapsed\/refractory (R\/R) multiple myeloma (MM). This open\u2010label, multicenter study had two distinct phases (phase one [P1], phase two [P2]). Patients in both phases received VenDex (oral Ven 800\u2009mg\/day + oral Dex 40\u2009mg [20\u2009mg for patients \u226575\u2009years] on days 1, 8, and 15, per 21\u2013day\u2009cycle). The primary objective of the P1 VenDex cohort was to assess safety and pharmacokinetics. Phase two further evaluated efficacy with objective response rate (ORR) and very good partial response or better. Correlative studies explored baseline <jats:italic>BCL2<\/jats:italic> (BCL\u20102) and <jats:italic>BCL2L1<\/jats:italic> (BCL\u2010X<jats:sub>L<\/jats:sub>) gene expression, cytogenetics, and recurrent somatic mutations in MM. Twenty and 31 patients in P1 and P2 with t(11;14) positive translocation received VenDex. P1\/P2 patients had received a median of 3\/5 lines of prior therapy, and 20%\/87% were refractory to daratumumab. Predominant grade 3\/4 hematological adverse events (AEs) with \u226510% occurrence included lymphopenia (20%\/19%), neutropenia (15%\/7%), thrombocytopenia (10%\/10%), and anemia (5%\/16%). At a median follow\u2010up of 12.3\/9.2 months, ORR was 60%\/48%. The duration of response estimate at 12\u2009months was 50%\/61%, and the median time to progression was 12.4\/10.8 months. In biomarker evaluable patients, response to VenDex was independent of concurrent del(17p) or gain(1q) and mutations in key oncogenic signaling pathways, including MAPK and NF\u2010kB. VenDex demonstrated efficacy and manageable safety in heavily\u2010pre\u2010treated patients with t(11;14) R\/R MM.<\/jats:p>","DOI":"10.1002\/ajh.26083","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T14:58:16Z","timestamp":1609167496000},"page":"418-427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Targeting <scp>BCL<\/scp>\u20102 with venetoclax and dexamethasone in patients with relapsed\/refractory t(11;14) multiple myeloma"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5687-6429","authenticated-orcid":false,"given":"Jonathan L.","family":"Kaufman","sequence":"first","affiliation":[{"name":"Winship Cancer Institute of Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Gasparetto","sequence":"additional","affiliation":[{"name":"Duke University, Hematologic Malignancies &amp; Cellular Therapy  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-0569","authenticated-orcid":false,"given":"Fredrik H.","family":"Schjesvold","sequence":"additional","affiliation":[{"name":"Oslo Myeloma Center, Oslo University Hospital, Oslo, Norway and K.G. 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South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Yang","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjiao","family":"Dunbar","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deeksha","family":"Vishwamitra","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Unger","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Macartney","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH &amp; Co KG  Wiesbaden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pesko","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yu","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Hamed","family":"Salem","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Ross","sequence":"additional","affiliation":[{"name":"AbbVie Inc  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Jen","family":"Hong","sequence":"additional","affiliation":[{"name":"Genentech Inc.  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