{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T12:39:41Z","timestamp":1766407181101,"version":"3.37.3"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T00:00:00Z","timestamp":1575417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T00:00:00Z","timestamp":1575417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report the final analysis of the PROLONG study on ofatumumab maintenance in relapsed chronic lymphocytic leukemia (CLL). In all, 480 patients with CLL in complete or partial remission after second- or third-line treatment were randomized 1:1 to ofatumumab (300\u2009mg first week, followed by 1000\u2009mg every 8 weeks for up to 2 years) or observation. Median follow-up duration was 40.9 months. Median progression-free survival was 34.2 and 16.9 months for ofatumumab and observation arms, respectively, (hazard ratio, 0.55 [95% confidence interval, 0.43\u20130.70]; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). Median time to next treatment for ofatumumab and observation arms, respectively, was 37.4 and 27.6 months (0.72 [0.57\u20130.91]; <jats:italic>P<\/jats:italic>\u2009=\u20090.0044). Overall survival was similar in both arms; median was not reached (0.99 [0.72\u20131.37]). Grade\u2009\u2265\u20093 adverse events occurred in 62% and 51% of patients in ofatumumab and observation arms, respectively, the most common being neutropenia (23% and 10%), pneumonia (13% and 12%) and febrile neutropenia (6% and 4%). Up to 60 days after the last treatment, four deaths were reported in the ofatumumab arm versus six in the observation arm, none considered related to ofatumumab. Ofatumumab maintenance significantly prolonged progression-free survival in patients with relapsed CLL and was well tolerated.<\/jats:p>","DOI":"10.1038\/s41408-019-0260-2","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T16:04:24Z","timestamp":1575475464000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Ofatumumab maintenance prolongs progression-free survival in relapsed chronic lymphocytic leukemia: final analysis of the PROLONG study"],"prefix":"10.1038","volume":"9","author":[{"given":"Marinus","family":"van Oers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Smolej","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Petrini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fritz","family":"Offner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2644-1050","authenticated-orcid":false,"given":"Sebastian","family":"Grosicki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark-David","family":"Levin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaclyn","family":"Davis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiya","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Stefanelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Hoever","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Geisler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"260_CR1","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1016\/S1470-2045(15)00143-6","volume":"16","author":"MH van Oers","year":"2015","unstructured":"van Oers, M. H. et al. Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukemia (PROLONG): an open-label, multicenter, randomized phase 3 study. Lancet Oncol. 16, 1370\u20131379 (2015).","journal-title":"Lancet Oncol."},{"key":"260_CR2","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1182\/blood-2007-06-093906","volume":"111","author":"M Hallek","year":"2008","unstructured":"Hallek, M. et al. International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 111, 5446\u20135456 (2008).","journal-title":"Blood"},{"key":"260_CR3","doi-asserted-by":"publisher","first-page":"e317","DOI":"10.1016\/S2352-3026(16)30045-X","volume":"3","author":"R Greil","year":"2016","unstructured":"Greil, R. et al. Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomized trial. Lancet Haematol. 3, e317\u2013e329 (2016).","journal-title":"Lancet Haematol."},{"key":"260_CR4","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1093\/jnci\/djr418","volume":"103","author":"L Vidal","year":"2011","unstructured":"Vidal, L. et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials. J. Natl. Cancer Inst. 103, 1799\u20131806 (2011).","journal-title":"J. Natl. Cancer Inst."},{"key":"260_CR5","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-014-0104-7","volume":"31","author":"BT Huang","year":"2014","unstructured":"Huang, B. T., Zeng, Q. C., Zhao, W. H., Li, B. S. & Chen, R. L. How to determine post-FCR therapy for cytogenetic risk-tailored elderly patients with chronic lymphocytic leukemia, maintenance rituximab or observation. Med. Oncol. 31, 104 (2014).","journal-title":"Med. Oncol."},{"key":"260_CR6","doi-asserted-by":"publisher","first-page":"e534","DOI":"10.1016\/S2352-3026(17)30168-0","volume":"4","author":"AA Chanan-Khan","year":"2017","unstructured":"Chanan-Khan, A. A. et al. Lenalidomide maintenance therapy in previously treated chronic lymphocytic leukemia (CONTINUUM): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 4, e534\u2013e543 (2017).","journal-title":"Lancet Haematol."},{"key":"260_CR7","doi-asserted-by":"publisher","first-page":"e475","DOI":"10.1016\/S2352-3026(17)30171-0","volume":"4","author":"AM Fink","year":"2017","unstructured":"Fink, A. M. et al. Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukemia (CLLM1): final results from a randomized, double-blind, phase 3 study. Lancet Haematol. 4, e475\u2013e486 (2017).","journal-title":"Lancet Haematol."},{"key":"260_CR8","doi-asserted-by":"publisher","first-page":"e82","DOI":"10.1016\/S2352-3026(17)30235-1","volume":"5","author":"C Dartigeas","year":"2018","unstructured":"Dartigeas, C. et al. Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomized phase 3 study. Lancet Haematol. 5, e82\u2013e94 (2018).","journal-title":"Lancet Haematol."},{"key":"260_CR9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1056\/NEJMoa1215637","volume":"369","author":"JC Byrd","year":"2013","unstructured":"Byrd, J. C. et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 369, 32\u201342 (2013).","journal-title":"N. Engl. J. Med."},{"key":"260_CR10","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","volume":"373","author":"JA Burger","year":"2015","unstructured":"Burger, J. A. et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N. Engl. J. Med. 373, 2425\u20132437 (2015).","journal-title":"N. Engl. J. Med."},{"key":"260_CR11","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1056\/NEJMoa1315226","volume":"370","author":"RR Furman","year":"2014","unstructured":"Furman, R. R. et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 370, 997\u20131007 (2014).","journal-title":"N. Engl. J. Med."},{"key":"260_CR12","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1513257","volume":"374","author":"AW Roberts","year":"2016","unstructured":"Roberts, A. W. et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 374, 311\u2013322 (2016).","journal-title":"N. Engl. J. Med."},{"key":"260_CR13","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S1470-2045(16)30019-5","volume":"17","author":"S Stilgenbauer","year":"2016","unstructured":"Stilgenbauer, S. et al. Venetoclax in relapsed or refractory chronic lymphocytic leukemia with 17p deletion: a multicenter, open-label, phase 2 study. Lancet Oncol. 17, 768\u2013778 (2016).","journal-title":"Lancet Oncol"},{"key":"260_CR14","doi-asserted-by":"publisher","first-page":"13906","DOI":"10.1073\/pnas.1409362111","volume":"111","author":"NL Komarova","year":"2014","unstructured":"Komarova, N. L., Burger, J. A. & Wodarz, D. Evolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL). Proc. Natl Acad. Sci. USA 111, 13906\u201313911 (2014).","journal-title":"Proc. Natl Acad. Sci. 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Oncol."}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0260-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0260-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0260-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T16:15:37Z","timestamp":1671207337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41408-019-0260-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,4]]},"references-count":16,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["260"],"URL":"https:\/\/doi.org\/10.1038\/s41408-019-0260-2","relation":{},"ISSN":["2044-5385"],"issn-type":[{"type":"electronic","value":"2044-5385"}],"subject":[],"published":{"date-parts":[[2019,12,4]]},"assertion":[{"value":"10 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2019","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.V.O. serves as a consulting or advisory role at Roche, ISA Therapeutics and Immunicum and provides expert testimony for Roche. L.S. and M.-D.L. have received honoraria, consulting fees and travel, accommodation and expenses from Roche, Janssen, AbbVie and Gilead. Both also served on speakers\u2019 bureau for Gilead. J.D. and P.H. are both employed by and hold stock or other ownership of Novartis. T.S. and H.B. are employees of Novartis. M.P., F.O., S.G., and C.G. have no relationships to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"98"}}