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We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-na\u00efve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https:\/\/Clinicaltrials.gov Identifier https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02315768).<\/jats:p>","DOI":"10.1155\/2022\/4450824","type":"journal-article","created":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T12:35:06Z","timestamp":1642854906000},"page":"1-8","source":"Crossref","is-referenced-by-count":4,"title":["Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b\/2 Clinical Trial NCT0231576"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2785-0892","authenticated-orcid":true,"given":"Januario E.","family":"Castro","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ, 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