PMID- 31628428 OWN - NLM STAT- MEDLINE DCOM- 20200824 LR - 20240328 IS - 1476-5551 (Electronic) IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 34 IP - 3 DP - 2020 Mar TI - Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. PG - 787-798 LID - 10.1038/s41375-019-0602-x [doi] AB - RESONATE-2 is a phase 3 study of first-line ibrutinib versus chlorambucil in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients aged >/=65 years (n = 269) were randomized 1:1 to once-daily ibrutinib 420 mg continuously or chlorambucil 0.5-0.8 mg/kg for /=3 adverse events (AEs) included neutropenia (13%), pneumonia (12%), hypertension (8%), anemia (7%), and hyponatremia (6%); occurrence of most events as well as discontinuations due to AEs decreased over time. Fifty-eight percent of patients continue to receive ibrutinib. Single-agent ibrutinib demonstrated sustained PFS and OS benefit versus chlorambucil and increased depth of response over time. FAU - Burger, Jan A AU - Burger JA AD - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA. jaburger@mdanderson.org. FAU - Barr, Paul M AU - Barr PM AD - Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. FAU - Robak, Tadeusz AU - Robak T AD - Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland. FAU - Owen, Carolyn AU - Owen C AD - Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada. FAU - Ghia, Paolo AU - Ghia P AUID- ORCID: 0000-0003-3750-7342 AD - Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Tedeschi, Alessandra AU - Tedeschi A AD - ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Bairey, Osnat AU - Bairey O AD - Rabin Medical Center, Petah Tikva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Hillmen, Peter AU - Hillmen P AD - The Leeds Teaching Hospitals, St. James Institute of Oncology, University of Leeds, Leeds, UK. FAU - Coutre, Steven E AU - Coutre SE AD - Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, USA. FAU - Devereux, Stephen AU - Devereux S AD - Kings College Hospital, NHS Foundation Trust, London, UK. FAU - Grosicki, Sebastian AU - Grosicki S AD - Department of Hematology and Cancer Prevention, Silesiam Medical University, Katowice, Poland. FAU - McCarthy, Helen AU - McCarthy H AD - Royal Bournemouth General Hospital, Bournemouth, UK. FAU - Simpson, David AU - Simpson D AD - North Shore Hospital, Auckland, New Zealand. FAU - Offner, Fritz AU - Offner F AD - Universitair Ziekenhuis Gent, Gent, Belgium. FAU - Moreno, Carol AU - Moreno C AD - Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. FAU - Dai, Sandra AU - Dai S AD - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA. FAU - Lal, Indu AU - Lal I AD - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA. FAU - Dean, James P AU - Dean JP AD - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA, USA. FAU - Kipps, Thomas J AU - Kipps TJ AD - UCSD Moores Cancer Center, San Diego, CA, USA. LA - eng GR - P30 CA016672/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191018 PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - 18D0SL7309 (Chlorambucil) RN - 1X70OSD4VX (ibrutinib) RN - JAC85A2161 (Adenine) SB - IM MH - Adenine/analogs & derivatives MH - Aged MH - Aged, 80 and over MH - Chlorambucil/administration & dosage MH - Disease-Free Survival MH - Drug Administration Schedule MH - Female MH - Follow-Up Studies MH - Humans MH - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy MH - Male MH - Patient Safety MH - Piperidines MH - Prognosis MH - Progression-Free Survival MH - Pyrazoles/*administration & dosage MH - Pyrimidines/*administration & dosage MH - Risk MH - Treatment Outcome PMC - PMC7214263 MID - NIHMS1571598 COIS- JAB reported honoraria and a consulting/advisory role with Janssen; speakers' bureau and travel expenses from Gilead, Janssen, Novartis, Pharmacyclics LLC, an AbbVie Company, and TG Therapeutics; and research funding from BeiGene, Gilead, Pharmacyclics LLC, an AbbVie Company, and TG Therapeutics. PMB reported a consultancy/advisory role for AbbVie and Pharmacyclics LLC, an AbbVie Company; and research funding from Pharmacyclics LLC, an AbbVie Company. TR reported research funding from Pharmacyclics LLC, an AbbVie company. CO reported honoraria from Gilead, Janssen, AbbVie, Roche, Merck, Teva, and AstraZeneca. PG reported honoraria from AbbVie, Acerta, BeiGene, Gilead, Roche, Sunesis, Celgene, and Janssen; a consultancy/advisory role from AbbVie, Acerta, BeiGene, Gilead, Janssen, Pharmacyclics LLC, an AbbVie Company, Celgene, and Sunesis; speakers' bureau for Gilead; and research funding from AbbVie, Gilead, Janssen, and Novartis. AT reported a consultancy/advisory role for Janssen spa, Gilead, Sunesis, and AbbVie; and speakers' bureau for Janssen. OB reported a consultancy/advisory role for AbbVie and research funding from Janssen. PH reported honoraria, a consultancy/advisory role, and research funding from Janssen, Pharmacyclics LLC, an AbbVie Company, and AbbVie; and travel expenses from Janssen and AbbVie. SEC reported honoraria from Pharmacyclics LLC, an AbbVie Company, and Janssen; a consultancy/advisory role for AbbVie, Astellas, AstraZeneca, Celgene, Genentech, Pharmacyclics LLC, an AbbVie Company, Novartis, and Janssen; travel, accommodations, expenses from AbbVie, BeiGene, Celgene, Genentech, Janssen, Pharmacyclics LLC, an AbbVie Company; expert testimony for Genentech; other relationship with BeiGene; and research funding from Celgene, Gilead, Janssen, Pharmacyclics LLC, an AbbVie Company, AbbVie, Takeda, and Acerta. SD reported a consultancy/advisory role for AbbVie, Janssen, GlaxoSmithKline, and Bristol-Myers Squibb; and speakers' bureau and travel expenses for Janssen and Gilead. HM reported honoraria and travel expenses from AbbVie, Janssen, Novartis, and Roche; and a consultancy/advisory role with Janssen. DS reported honoraria from Celgene, Roche, MSD, and Janssen; travel expenses from Celgene, Bristol-Myers Squibb, Janssen, and Novartis; and research funding from Amgen, MSD, Pharmacyclics LLC, an AbbVie Company, AbbVie, Sanofi, Roche, BeiGene, and Acerta. CM reported a consulting/advisory role with Pharmacyclics LLC, an AbbVie Company, Janssen, and AbbVie. SD reported employment with Pharmacyclics LLC, an AbbVie Company; and stock ownership with AbbVie, Celgene, Gilead, GSK, and Exelixis. IL reported employment with Pharmacyclics, an AbbVie Company, and spouse employment with The Permanente Medical Group; and stock ownership with AbbVie, Gilead Sciences, Clovis, Infinity, The Permanente Medical Group, and Reviva Pharmaceuticals. JPD reported employment with Pharmacyclics LLC, an AbbVie Company, and CTI BioPharma Corp; and stock ownership with AbbVie and CTI BioPharma Corp. TJK reported a consultancy/advisory role for AbbVie, Genentech-Roche, Gilead, Pharmacyclics LLC, an AbbVie Company, and Celgene; and research funding from AbbVie, Genentech-Roche, Pharmacyclics LLC, an AbbVie Company, and Oncternal. SG and FO reported no relevant financial disclosures. EDAT- 2019/10/20 06:00 MHDA- 2020/08/25 06:00 PMCR- 2019/10/18 CRDT- 2019/10/20 06:00 PHST- 2019/04/11 00:00 [received] PHST- 2019/08/22 00:00 [accepted] PHST- 2019/08/08 00:00 [revised] PHST- 2019/10/20 06:00 [pubmed] PHST- 2020/08/25 06:00 [medline] PHST- 2019/10/20 06:00 [entrez] PHST- 2019/10/18 00:00 [pmc-release] AID - 10.1038/s41375-019-0602-x [pii] AID - 602 [pii] AID - 10.1038/s41375-019-0602-x [doi] PST - ppublish SO - Leukemia. 2020 Mar;34(3):787-798. doi: 10.1038/s41375-019-0602-x. Epub 2019 Oct 18.