{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:19:35Z","timestamp":1765354775940,"version":"3.37.3"},"reference-count":40,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Fifty-one of 189 evaluable patients from 3 prospective phase 2 trials evaluating a sequential targeted treatment had high-risk chronic lymphocytic leukemia (CLL) with a 17p deletion, TP53 mutation, or both. Twenty-seven patients started treatment with bendamustine debulking before induction and maintenance treatment, which was ibrutinib\/ofatumumab (IO) in 21 patients, ibrutinib\/obinutuzumab (IG) in 13, and venetoclax\/obinutuzumab (AG) in 17. The primary end point was overall response rate after 8 months of induction treatment, which was 81%, 100%, and 94% for IO, IG, and AG, respectively. Minimal residual disease (MRD) was undetectable (uMRD) in peripheral blood (&amp;lt;10\u22124 by flow cytometry) in 0%, 23%, and 82% of patients, respectively. Median progression-free survival (PFS) was 45 months. Seventeen patients discontinued maintenance treatment due to uMRD: 9 progressed, 2 died without progression (median PFS, 28 months after discontinuation of treatment), and 6 remained in remission after a median observation time of 46 months (range, 6-47 months) after treatment discontinuation. Thus, MRD-guided fixed-duration therapies combining obinutuzumab with venetoclax or ibrutinib can induce deep and durable remissions in CLL patients with high-risk genetic lesions, which can persist after treatment discontinuation (due to a predefined fixed-duration or MRD-guided early termination). The median PFS was 45 months. These trials were registered at www.clinicaltrials.gov as #NCT02345863, #NCT02401503, and #NCT02689141.<\/jats:p>","DOI":"10.1182\/blood.2020010484","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T21:09:04Z","timestamp":1622840944000},"page":"1805-1816","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":14,"title":["Durable remissions following combined targeted therapy in patients with CLL harboring <i>TP53<\/i> deletions and\/or mutations"],"prefix":"10.1182","volume":"138","author":[{"given":"Paula","family":"Cramer","sequence":"first","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugen","family":"Tausch","sequence":"additional","affiliation":[{"name":"Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"von Tresckow","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"},{"name":"Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany;"},{"name":"Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Giza","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Robrecht","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christof","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz","family":"F\u00fcrstenau","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6654-0304","authenticated-orcid":false,"given":"Petra","family":"Langerbeins","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Othman","family":"Al-Sawaf","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt W.","family":"Pelzer","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Fink","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and German CLL Study Group, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO 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