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Patients were randomized to 2 years of VenR (n = 194; rituximab for the first 6 months) or 6 months of BR (n = 195). Although undetectable minimal residual disease (uMRD) was achieved more often with VenR, the long-term implications of uMRD with this fixed-duration, chemotherapy-free regimen have not been explored. We report MRD kinetics and updated outcomes with 5 years\u2019 follow-up. Survival benefits with VenR vs BR were sustained (median PFS [95% confidence interval]: 53.6 [48.4, 57.0] vs 17.0 [15.5, 21.7] months, respectively, P &amp;lt; .0001; 5-year OS [95% confidence interval]: 82.1% [76.4, 87.8] vs 62.2% [54.8, 69.6], P &amp;lt; .0001). VenR was superior to BR, regardless of cytogenetic category. VenR-treated patients with uMRD at end of treatment (EOT; n = 83) had superior OS vs those with high-MRD+ (n = 12): 3-year post-EOT survival rates were 95.3% vs 72.9% (P = .039). In those with uMRD at EOT, median time to MRD conversion was 19.4 months. Of 47 patients with documented MRD conversion, 19 developed progressive disease (PD); median time from conversion to PD was 25.2 months. A population-based logistic growth model indicated slower MRD median doubling time post-EOT with VenR (93 days) vs BR (53 days; P = 1.2 \u00d7 10\u22127). No new safety signals were identified. Sustained survival, uMRD benefits, and durable responses support 2-year fixed-duration VenR treatment in R\/R CLL.<\/jats:p>","DOI":"10.1182\/blood.2021015014","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T15:55:26Z","timestamp":1653321326000},"page":"839-850","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":159,"title":["Enduring undetectable MRD and updated outcomes in relapsed\/refractory CLL after fixed-duration venetoclax-rituximab"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-6835","authenticated-orcid":false,"given":"John F.","family":"Seymour","sequence":"first","affiliation":[{"name":"1Peter MacCallum Cancer Centre, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarit","family":"Assouline","sequence":"additional","affiliation":[{"name":"6Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Lamanna","sequence":"additional","affiliation":[{"name":"7Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-6357","authenticated-orcid":false,"given":"Tadeusz","family":"Robak","sequence":"additional","affiliation":[{"name":"8Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3904-1101","authenticated-orcid":false,"given":"Javier","family":"de la Serna","sequence":"additional","affiliation":[{"name":"9Hospital Universitario 12 de Octubre, Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9826-1062","authenticated-orcid":false,"given":"Ulrich","family":"Jaeger","sequence":"additional","affiliation":[{"name":"10Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0659-9635","authenticated-orcid":false,"given":"Guillaume","family":"Cartron","sequence":"additional","affiliation":[{"name":"11Department of Hematology, Centre Hospitalier Universitaire de Montpellier (UMR-CNRS 5535), Montpellier, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Montillo","sequence":"additional","affiliation":[{"name":"12Department of Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Mellink","sequence":"additional","affiliation":[{"name":"13Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Chyla","sequence":"additional","affiliation":[{"name":"14AbbVie, North Chicago, IL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anesh","family":"Panchal","sequence":"additional","affiliation":[{"name":"15Roche Products Ltd., Welwyn Garden City, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-6857","authenticated-orcid":false,"given":"Tong","family":"Lu","sequence":"additional","affiliation":[{"name":"16Genentech, Inc., South San Francisco, CA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny 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