{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:56:41Z","timestamp":1780639001840,"version":"3.54.1"},"reference-count":55,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,18]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>The phase 2 CLL2-BAAG trial tested the measurable residual disease (MRD)\u2013guided triple combination of acalabrutinib, venetoclax, and obinutuzumab after optional bendamustine debulking in 45 patients with relapsed\/refractory chronic lymphocytic leukemia (CLL). MRD was measured by flow cytometry (FCM; undetectable MRD &amp;lt;10\u20134) in peripheral blood (PB) and circulating tumor DNA (ctDNA) using digital droplet polymerase chain reaction of variable-diversity-joining (VDJ) rearrangements and CLL-related mutations in plasma. The median number of previous treatments was 1 (range, 1-4); 18 patients (40%) had received a Bruton tyrosine kinase inhibitor (BTKi) and\/or venetoclax before inclusion, 14 of 44 (31.8%) had TP53 aberrations, and 34 (75.6%) had unmutated immunoglobulin heavy-chain variable region genes. With a median observation time of 36.3 months and all patients off-treatment for a median of 21.9 months, uMRD &amp;lt;10\u20134 in PB was achieved in 42 of the 45 patients (93.3%) at any time point, including 17 of 18 (94.4%) previously exposed to venetoclax\/BTKi and 13 of 14 (92.9%) with TP53 aberrations. The estimated 3-year progression-free and overall survival rates were 85.0% and 93.8%, respectively. Overall, 585 paired FCM\/ctDNA samples were analyzed and 18 MRD recurrences (5 with and 13 without clinical progression) occurred after the end of treatment. Twelve samples were first detected by ctDNA, 3 by FCM, and 3 synchronously. In conclusion, time-limited MRD-guided acalabrutinib, venetoclax, and obinutuzumab achieved deep remissions in almost all patients with relapsed\/refractory CLL. The addition of ctDNA-based analyses to FCM MRD assessment seems to improve early detection of relapses. This trial was registered at www.clinicaltrials.gov as #NCT03787264.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023022730","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T18:11:12Z","timestamp":1713204672000},"page":"272-282","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":23,"title":["Acalabrutinib, venetoclax, and obinutuzumab in relapsed\/refractory CLL: final efficacy and ctDNA analysis of the CLL2-BAAG trial"],"prefix":"10.1182","volume":"144","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 of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German Chronic Lymphocytic Leukemia Study Group, University of Cologne, Cologne, 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