{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:27:35Z","timestamp":1789964855762,"version":"4.0.1"},"reference-count":68,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"36","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Society of Clinical Oncology Educational Book"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>During the past 5 years, rapid therapeutic advances have changed the landscape of chronic lymphocytic leukemia (CLL) therapy. This disease has traditionally been treated using cytotoxic chemotherapy regimens in combination with anti-CD20 antibody treatment, and recent long-term follow-up data from multiple centers suggest that fit patients with CLL with favorable disease features\u2014particularly mutated immunoglobulin heavy chain variable region ( IGHV) genes\u2014derive very long-term benefit from the most potent of these regimens, namely the fludarabine, cyclophosphamide, and rituximab (FCR) regimen. The advent of oral targeted therapies, particularly ibrutinib and idelalisib, has provided generally well-tolerated and highly effective additional options that have come into widespread use in the relapsed setting. Additional agents are advancing in clinical development, with the BCL-2 inhibitor venetoclax likely to be approved by the U.S. Food and Drug Administration (FDA) in 2016. With the development of these novel therapies for patients with relapsed CLL, many unanswered questions remain, including the optimal sequence (first vs. second line), duration, discontinuation, and combination of these agents. In addition, recent publications show the emergence of a pattern of treatment resistance in certain subgroups of patients with del(17p) and complex karyotype that needs further study and improvement. Because the field of CLL management has become much more complex, we focus here on understanding the recent data and discuss many of the questions and controversies important for how we approach patients with CLL.<\/jats:p>","DOI":"10.1200\/edbk_159018","type":"journal-article","created":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T13:46:40Z","timestamp":1540820800000},"page":"e387-e398","source":"Crossref","is-referenced-by-count":32,"title":["Chemoimmunotherapy Versus Targeted Treatment in Chronic Lymphocytic Leukemia: When, How Long, How Much, and in Which Combination?"],"prefix":"10.1200","author":[{"given":"Jennifer R.","family":"Brown","sequence":"first","affiliation":[{"name":"From the Dana-Farber Cancer Institute, Boston, MA; University Hospital of Cologne, Cologne, Germany; Swedish Cancer Institute, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Hallek","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, Boston, MA; University Hospital of Cologne, Cologne, Germany; Swedish Cancer Institute, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Pagel","sequence":"additional","affiliation":[{"name":"From the Dana-Farber Cancer Institute, Boston, MA; University Hospital of Cologne, Cologne, Germany; Swedish Cancer Institute, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"bibr1-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093906"},{"key":"bibr2-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.10.861"},{"key":"bibr3-EDBK_159018","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1159\/000443013","volume":"39","author":"Langerbeins P","year":"2016","journal-title":"Oncol Res 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Serum chemokines and cytokines in CLL patients treated with duvelisib, a PI3K-{delta},{gamma} inhibitor.\n                      J Clin Oncol\n                      . 2015;33:15s (suppl; abstr 7072).","DOI":"10.1200\/jco.2015.33.15_suppl.7072"},{"key":"bibr66-EDBK_159018","first-page":"334)","volume":"124","author":"O\u2019Brien SM","year":"2014","journal-title":"Blood"},{"key":"bibr67-EDBK_159018","first-page":"154","volume":"100","author":"Burris HA","year":"2015","journal-title":"Haematologica"},{"key":"bibr69-EDBK_159018","doi-asserted-by":"crossref","first-page":"86)","DOI":"10.1182\/blood.V122.21.86.86","volume":"122","author":"Brown JR","year":"2013","journal-title":"Blood"},{"key":"bibr70-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.34.7898"},{"key":"bibr71-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"bibr72-EDBK_159018","doi-asserted-by":"crossref","first-page":"311-322","DOI":"10.1056\/NEJMoa1513257","volume":"374","author":"Roberts AW","year":"2016","journal-title":"N Engl J Med"},{"key":"bibr74-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.021"},{"key":"bibr78-EDBK_159018","first-page":"1146","volume":"26","author":"Jain P","year":"2012","journal-title":"Oncology (Williston Park)"},{"key":"bibr81-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305133"},{"key":"bibr82-EDBK_159018","doi-asserted-by":"crossref","first-page":"e35178","DOI":"10.1371\/journal.pone.0035178","volume":"7","author":"Grzywnowicz M","year":"2012","journal-title":"PLoS One"},{"key":"bibr84-EDBK_159018","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1182\/blood-2015-02-626754","volume":"126","author":"McClanahan F","year":"2015","journal-title":"Blood"},{"key":"bibr86-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.06.004"},{"key":"bibr87-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60027-7"},{"key":"bibr88-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.3187"},{"key":"bibr89-EDBK_159018","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-512137"},{"key":"bibr90-EDBK_159018","unstructured":"Robak T, Hellmann A, Kloczko J, et al. Randomized phase 2 study of otlertuzumab (TRU-016) and bendamustine vs bendamustine in patients with relapsed chronic lymphocytic leukemia. In press."}],"container-title":["American Society of Clinical Oncology Educational Book"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/EDBK_159018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T05:19:01Z","timestamp":1653801541000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/EDBK_159018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5]]},"references-count":68,"aliases":["10.14694\/edbk_159018"],"journal-issue":{"issue":"36","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1200\/EDBK_159018"],"URL":"https:\/\/doi.org\/10.1200\/edbk_159018","relation":{},"ISSN":["1548-8748","1548-8756"],"issn-type":[{"value":"1548-8748","type":"print"},{"value":"1548-8756","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5]]}}}