{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:36:30Z","timestamp":1788482190089,"version":"build-2803163510"},"reference-count":39,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,3,20]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The phase 2 CLL2-BZAG trial tested a measurable residual disease (MRD)\u2013guided combination treatment of zanubrutinib, venetoclax, and obinutuzumab after an optional bendamustine debulking in patients with relapsed\/refractory chronic lymphocytic leukemia (CLL). In total, 42 patients were enrolled and 2 patients with \u22642 induction cycles were excluded from the analysis population per protocol. Patients had a median of 1 prior therapy (range, 1-5); 18 patients (45%) had already received a Bruton tyrosine kinase (BTK) inhibitor (BTKi); 7 patients (17.5%) venetoclax; and, of these, 5 (12.5%) had received both. Fifteen patients (37.5%) had a TP53 mutation\/deletion, and 31 (77.5%) had unmutated immunoglobulin heavy chain variable region gene. With a median observation time of 21.5 months (range, 8.0-35.3) the most common adverse events were COVID-19 (n\u00a0=\u00a026 patients), diarrhea (n\u00a0=\u00a015), infusion-related reactions (n\u00a0=\u00a015), thrombocytopenia (n\u00a0=\u00a014), nausea (n\u00a0=\u00a012), fatigue (n\u00a0=\u00a012), and neutropenia (n\u00a0=\u00a012). Two patients had fatal adverse events (COVID-19, and fungal pneumonia secondary to COVID-19). After 6\u00a0months of the triple combination, all patients responded, and 21 (52.5%; 95% confidence interval, 36.1-68.5) showed undetectable MRD (uMRD) in the peripheral blood. In many patients, remissions deepened over time, with a best uMRD rate of 85%. The estimated progression-free and overall survival rates at 18 months were 96% and 96.8%, respectively. No patient has yet required a subsequent treatment. In summary, the MRD-guided triple combination of zanubrutinib, venetoclax, and obinutuzumab induced deep remissions in a relapsed CLL population enriched for patients previously treated with a BTKi\/venetoclax. This trial was registered at www.clinicaltrials.gov as #NCT04515238.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024026685","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T16:56:57Z","timestamp":1738256217000},"page":"1282-1292","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":10,"title":["MRD-guided zanubrutinib, venetoclax, and obinutuzumab in relapsed CLL: primary end point analysis from the CLL2-BZAG trial"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-0140","authenticated-orcid":false,"given":"Moritz","family":"F\u00fcrstenau","sequence":"first","affiliation":[{"name":"1Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German Chronic Lymphocytic Leukemia Study Group, University of Cologne, Cologne, 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