{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:22:48Z","timestamp":1791638568801,"version":"4.3.4"},"reference-count":26,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"36","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,12,20]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> The CLL14 study has established one-year fixed-duration treatment of venetoclax and obinutuzumab (Ven-Obi) for patients with previously untreated chronic lymphocytic leukemia. With all patients off treatment for at least three years, we report a detailed analysis of minimal residual disease (MRD) kinetics and long-term outcome of patients treated in the CLL14 study. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Patients were randomly assigned to receive six cycles of obinutuzumab with 12 cycles of venetoclax or 12 cycles of chlorambucil (Clb-Obi). Progression-free survival (PFS) was the primary end point. Key secondary end points included rates of undetectable MRD and overall survival. To analyze MRD kinetics, a population-based growth model with nonlinear mixed effects approach was developed. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Of 432 patients, 216 were assigned to Ven-Obi and 216 to Clb-Obi. Three months after treatment completion, 40% of patients in the Ven-Obi arm (7% in the Clb-Obi arm) had undetectable MRD levels &lt; 10<jats:sup>\u22126<\/jats:sup> by next-generation sequencing in peripheral blood. Median MRD doubling time was longer after Ven-Obi than Clb-Obi therapy (median 80 v 69 days). At a median follow-up of 52.4 months, a sustained significant PFS improvement was observed in the Ven-Obi arm compared with Clb-Obi (median not reached v 36.4 months; hazard ratio 0.33; 95% CI, 0.25 to 0.45; P &lt; .0001). The estimated 4-year PFS rate was 74.0% in the Ven-Obi and 35.4% in the Clb-Obi arm. No difference in overall survival was observed (hazard ratio 0.85; 95% CI, 0.54 to 1.35; P = .49). No new safety signals occurred. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Appearance of MRD after Ven-Obi is significantly slower than that after Clb-Obi with more effective MRD reduction. These findings translate into a superior long-term efficacy with the majority of Ven-Obi\u2013treated patients remaining in remission. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.21.01181","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T19:59:37Z","timestamp":1635451177000},"page":"4049-4060","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":140,"title":["Minimal Residual Disease Dynamics after Venetoclax-Obinutuzumab Treatment: Extended Off-Treatment Follow-up From the Randomized CLL14 Study"],"prefix":"10.1200","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9895-0570","authenticated-orcid":false,"given":"Othman","family":"Al-Sawaf","sequence":"first","affiliation":[{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, German CLL Study Group, Center for Integrated Oncology Aachen Bonn Cologne D\u00fcsseldorf, Germany"},{"name":"The Francis Crick Institute, London, United Kingdom"},{"name":"UCL Cancer Institute, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, German CLL Study Group, Center for Integrated Oncology Aachen Bonn Cologne D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-6857","authenticated-orcid":false,"given":"Tong","family":"Lu","sequence":"additional","affiliation":[{"name":"Genentech, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Z.","family":"Liao","sequence":"additional","affiliation":[{"name":"Genentech, San Francisco, 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