{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:20:13Z","timestamp":1792516813315,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immune dysregulation is a hallmark of chronic lymphocytic leukemia (CLL). Anti\u2010CD20 antibodies (e.g., rituximab [R]) can be combined with venetoclax (Ven) to treat CLL. However, anti\u2010CD20 antibodies can increase hypogammaglobulinemia risk, while the effects of Ven on immune dysregulation are still uncertain. We report long\u2010term immune changes in VenR\u2010 and bendamustine\u2010R (BR)\u2010treated patients with relapsed\/refractory CLL in the MURANO trial (NCT02005471). Patients were randomized to fixed\u2010duration VenR (2 years Ven; VenR for the first 6 months) or BR (6 months). Immune cell levels were evaluated at the end of combination treatment (EOCT), end of treatment (EOT; VenR arm only), and 12 and 24 months post\u2010EOCT. Overall, 130\/194 VenR\u2010 and 134\/195 BR\u2010treated patients completed treatment without progressive disease. In patients who completed VenR combination therapy, median immunoglobulin (Ig)G and IgM levels decreased from baseline to EOT (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.01 and <jats:italic>p<\/jats:italic>\u2009\u2264\u20090.0001, respectively); by 24 months, post\u2010EOT IgG had returned to baseline level and IgM had increased from baseline (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001). Median IgA levels increased from baseline to 12 (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.0001) and 24 months post\u2010EOT (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.0001). In BR\u2010treated patients, changes in IgG, IgA, and IgM levels across the assessed time points were not significant, and by 24 months, post\u2010EOCT IgG, IgA, and IgM were above baseline levels. Grade \u22653 infection rates on treatment were low. Overall, immune recovery was observed with VenR and BR, with stabilization of Ig levels after treatment. Post\u2010treatment infection rates were generally low, making these very tolerable therapies for CLL.<\/jats:p>","DOI":"10.1002\/hem3.146","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T10:20:10Z","timestamp":1724754010000},"source":"Crossref","is-referenced-by-count":5,"title":["Long\u2010term immune changes in patients with relapsed\/refractory chronic lymphocytic leukemia following treatment with venetoclax plus rituximab"],"prefix":"10.1002","volume":"8","author":[{"given":"Arnon P.","family":"Kater","sequence":"first","affiliation":[{"name":"Department of Hematology, Cancer Center Amsterdam, LYMMCARE, Amsterdam University Medical Centers University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara F.","family":"Eichhorst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Center of Integrated Oncology Aachen, Bonn, Cologne, Dusseldorf (CIO ABCD), Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn J.","family":"Owen","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Oncology University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Jaeger","sequence":"additional","affiliation":[{"name":"Clinical Department of Hematology and Hemostaseology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Chyla","sequence":"additional","affiliation":[{"name":"AbbVie North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Lefebure","sequence":"additional","affiliation":[{"name":"Roche Products Ltd Welwyn Garden City UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Millen","sequence":"additional","affiliation":[{"name":"Roche Products Ltd Welwyn Garden City UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Genentech Inc. South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Thadani\u2010Mulero","sequence":"additional","affiliation":[{"name":"Roche Products Ltd Welwyn Garden City UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Boyer","sequence":"additional","affiliation":[{"name":"Roche Products Ltd Welwyn Garden City UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Seymour","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Centre Royal Melbourne Hospital and University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1992.tb01805.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1992.tb06965.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-9995-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02115-1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.600829"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-567388"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-01817-z"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200108000-00002"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15722"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0759"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-116405"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004861"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203317719334"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022008221"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000360"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12665"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713976"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021015014"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000360"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010236"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1772477"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-142763"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5971-z"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.126763"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1657575"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-022-02170-w"}],"container-title":["HemaSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hem3.146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T13:30:39Z","timestamp":1724765439000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hem3.146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/hem3.146"],"URL":"https:\/\/doi.org\/10.1002\/hem3.146","archive":["Portico"],"relation":{},"ISSN":["2572-9241","2572-9241"],"issn-type":[{"value":"2572-9241","type":"print"},{"value":"2572-9241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]},"article-number":"e146"}}