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Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) \u2265 2 on\/after 1\/1\/2014 was followed between 1\/2007 and 3\/2018 in Optum\u2019s deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, <jats:italic>n<\/jats:italic> = 349; KRd, <jats:italic>n<\/jats:italic> = 218; DRd, <jats:italic>n<\/jats:italic> = 99; IRd, <jats:italic>n<\/jats:italic> = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, <jats:italic>n<\/jats:italic> = 52; KPd, <jats:italic>n<\/jats:italic> = 146; DPd, <jats:italic>n<\/jats:italic> = 149; IPd, <jats:italic>n<\/jats:italic> = 45) in LOTs \u22652 were identified. More patients \u226575 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd\/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT \u2265 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation\/death (HR 1.72; <jats:italic>P<\/jats:italic> = 0.0142); no Pd triplet was significantly different vs DPd in LOT \u2265 2. Our data highlight important efficacy\/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.<\/jats:p>","DOI":"10.1007\/s00277-021-04534-8","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T04:02:42Z","timestamp":1620619362000},"page":"2325-2337","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed\/refractory multiple myeloma (RRMM) in the US"],"prefix":"10.1007","volume":"100","author":[{"given":"Faith","family":"Davies","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rifkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Costello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Usmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafat","family":"Abonour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy","family":"Romanus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Hajek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Terpos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dasha","family":"Cherepanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn Marie","family":"Stull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Leleu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Berdeja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans C.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Boccadoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Zonder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Puig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Vela-Ojeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Farrelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Raju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlo","family":"Blazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajai","family":"Chari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"4534_CR1","unstructured":"ASCO. 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Expert Rev Hematol 13(4):421\u2013433","journal-title":"Expert Rev Hematol"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04534-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-021-04534-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04534-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T05:06:35Z","timestamp":1628658395000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-021-04534-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,10]]},"references-count":29,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["4534"],"URL":"https:\/\/doi.org\/10.1007\/s00277-021-04534-8","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,10]]},"assertion":[{"value":"8 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Advarra Institutional Review Board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"FD reports honoraria from Adaptive, Celgene Corporation, Janssen, Oncopeptide, Roche, Sanofi, and Takeda; consultancy or research funding from Celgene Corporation, Janssen, Oncopeptide, Roche, Sanofi, and Takeda. RR is a current equity holder in McKesson; advisory board member for Takeda, Amgen, and BMS (Celgene); investigator for AbbVie; and consultancy for Takeda, Amgen, Celgene, BMS, Mylan, Coherus, BioSciences, and Fresenius. CC receives grants and honorarium from Takeda and BMS and honorarium from Karyopharm and Oncopeptides. GM has received funding from Celgene, BMS, Sanofi, Karyopharm, Janssen, Roche, and Genentech. SU receives research funding from Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, and Takeda; SU receives consulting fees from Abbvie, Amgen, BMS, Celgene, GSK, Genentech\/Roche, Janssen, Karyopharm, Merck, Oncopeptides, Sanofi, Seattle Genetics, SkylineDx, and Takeda; SU receives speaking fees from Celgene, Janssen, Sanofi, and Takeda. RA reports grants from Takeda. AP is an employee of GSK. DC, DMS, HH, and DR are or were all employees of Millennium Pharmaceuticals, Inc., a wholly own subsidiary of Takeda Pharmaceutical Company Limited, at the time this research was conducted. RH receives consulting honoraria and\/or research support received from Takeda, Novartis, Celgene, PharmaMar, Oncopeptides, Janssen, Amgen, AbbVie, and Bristol-Myers Squibb. ET declares honoraria from Amgen, BMS, Janssen, Celgene, Takeda, Genesis Pharma, and Sanofi and research funding from Janssen, Amgen, Sanofi, Takeda, and Genesis Pharma. XL receives honoraria from Takeda, Janssen, BMS, Sanofi, Magen, Oncopeptide, Karyopharm, Novartis, and Merck. JB receives research funding from Abbvie, Amgen, Acetylon, Bluebird, BMS, Celgene, Celularity, Constellation, CRISP Therapeutics, CURIS, EMD Sorono, Genentech, Glenmark, Ichnos, Janssen, Kesios, Lilly, Novartis, Poseida, Sanofi, Takeda, Teva, Vivolux. JB receives consultancy payments from Amgen, BioClinica, Bluebird, BMS, Celgene, CRISPR Therapeutics, Janssen, Karyopharm, Kite Pharma, Legend, Prothena, SecuraBio, and Servier. HCL reports consulting or advisory role for Takeda, Celgene, Adaptive Biotechnologies, Amgen, GSK, Sanofi, and Janssen; research funding from Takeda, Amgen, Daiichi Sankyo, Janssen, Celgene and GSK. KW reports grants from Amgen, Celgene, Sanofi, Janssen (all to the institution), honoraria and advisory board from Amgen, BMS, Celgene, Adaptive Biotech, Janssen, GSK, Karyopharm, Roche, Sanofi, Takeda, and Oncopeptides. MT is an advisor\/consultant for Adaptive, BMS, Doximity, Elsevier, GRAIL\/Ilumina, Syapse Precision Medicine Council, Takeda, and UpToDate. He receives research funding from AbbVie, Amgen, BMS, CRAB CTC, Denovo, GSK, Hoosier Research Network, Janssen, Lilly, LynxBio, Strata Oncology, Takeda, and TG Therapeutics. MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and AbbVie; has served on the advisory boards for Janssen and GSK; has received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and Mundipharma. JAZ reports consultancy or advisory role for Celgene, BMS, Prothena, Janssen, Amgen, Takeda, Caelum Biosciences, Intellia Therapeutics, Alnylam and Oncotherapeutics; institutional research funding from Celgene and BMS. GC receives grant\/research support from Celgene\/BMS, Janssen, and Takeda and honoraria from Amgen, BMS, Celgene, Janssen, Takeda, Roche, GSK, Oncopeptides, and Sanofi. NP reports consulting or advisory role for Takeda, Amgen, Celgene, and Janssen; speaker\u2019s bureau for Celgene; honoraria from Takeda, Amgen, Celgene, Janssen, and The Binding Site; travel, accommodation, expenses and research funding from Celgene, Janssen, Amgen, and Takeda. EF, AR, and MB are or were employees of Xcenda, LLC at the time research was conducted; AC reports grants and personal fees from Janssen, grants and personal fees from Celgene, grants and personal fees from Novartis Pharmaceuticals, grants and personal fees from Amgen, personal fees from Bristol Myers Squibb, grants from Pharmacyclics, personal fees from Karyopharm, personal fees from Sanofi, grants and personal fees from Seattle Genetics, personal fees from Oncopeptides, grants and personal fees from Millenium\/Takeda, personal fees from Antengene, personal fees from GlaxoSmithKline, and personal fees from Secura Bio. No further conflicts are reported by the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}