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Haematologica 2018 Volume 103(9):1502-1510
Ferrata Storti Foundation
Chronic Lymphocytic Leukemia
Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2
Paul M. Barr,1 Tadeusz Robak,2 Carolyn Owen,3 Alessandra Tedeschi,4
Osnat Bairey,5,6 Nancy L. Bartlett,7 Jan A. Burger,8 Peter Hillmen,9
Steven Coutre,10 Stephen Devereux,11 Sebastian Grosicki,12 Helen McCarthy,13 Jianyong Li,14 David Simpson,15 Fritz Offner,16 Carol Moreno,17 Cathy Zhou,18 Lori Styles,18 Danelle James,18 Thomas J. Kipps19 and Paolo Ghia20
1University of Rochester, NY, USA; 2Medical University of Lodz, Poland; 3Tom Baker Cancer Centre, Calgary, AB, Canada; 4ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 5Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel; 6Sackler Faculty of Medicine, Tel Aviv University, Israel; 7Washington University School of Medicine, St. Louis, MO, USA; 8University of Texas MD Anderson Cancer Center, Houston, TX, USA; 9The Leeds Teaching Hospitals, St. James Institute of Oncology, UK; 10Stanford University School of Medicine, CA, USA; 11Kings College Hospital, NHS Foundation Trust, London, UK; 12School of Public Health, Silesian Medical University, Katowice, Poland; 13Royal Bournemouth Hospital, UK; 14Jiangsu Province Hospital, Nanjing, China; 15North Shore Hospital, Auckland, New Zealand; 16Universitair Ziekenhuis Gent, Belgium; 17Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 18Pharmacyclics, LLC, an AbbVie Company, Sunnyvale, CA, USA; 19University of California, San Diego, Moores Cancer Center, La Jolla, CA, USA and 20Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele, Milan, Italy
ABSTRACT
Results of RESONATE-2 (PCYC-1115/1116) supported approval of ibrutinib for first-line treatment of chronic lymphocytic leukemia. Extended analysis of RESONATE-2 was conducted to determine long-term efficacy and safety of ibrutinib in older patients with chronic lymphocytic leukemia. A total of 269 patients aged ≥65 years with previously untreated chronic lymphocytic leukemia with- out del(17p) were randomized 1:1 to ibrutinib (n=136) or chlorambucil (n=133) on days 1 and 15 of a 28-day cycle for 12 cycles. Median ibru- tinib treatment duration was 28.5 months. Ibrutinib significantly pro- longed progression-free survival versus chlorambucil (median, not reached vs. 15 months; hazard ratio, 0.12; 95% confidence interval, 0.07-0.20; P<0.0001). The 24-month progression-free survival was 89% with ibrutinib (97% and 89% in patients with del[11q] and unmutated immunoglobulin heavy chain variable region gene, respec- tively). Progression-free survival rates at 24 months were also similar regardless of age (<75 years [88%], ≥75 years [89%]). Overall response rate was 92% (125/136). Rate of complete response increased substan- tially from 7% at 12 months to 18% with extended follow up. Greater quality of life improvements occurred with ibrutinib versus chlorambu- cil in Functional Assessment of Chronic Illness Therapy-Fatigue (P=0.0013). The most frequent grade ≥3 adverse events were neutrope- nia (12%), anemia (7%), and hypertension (5%). Rate of discontinua- tions due to adverse events was 12%. Results demonstrated that first- line ibrutinib for elderly patients with chronic lymphocytic leukemia provides sustained response and progression-free survival benefits over chemotherapy, with depth of response improving over time without new toxicity concerns. This trial was registered at clinicaltrials.gov iden- tifier 01722487 and 01724346.
Correspondence:
Paul_Barr@URMC.Rochester.edu
Received: February 28, 2018. Accepted: June 4, 2018. Pre-published: June 7, 2018.
doi:10.3324/haematol.2018.192328
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/9/1502
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