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Haematologica. 2018 Sep;103(9):1502-1510. doi: 10.3324/haematol.2018.192328. Epub 2018 Jun 7.

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.

Author information

1
University of Rochester, NY, USA Paul_Barr@URMC.Rochester.edu.
2
Medical University of Lodz, Poland.
3
Tom Baker Cancer Centre, Calgary, AB, Canada.
4
ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
5
Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
6
Sackler Faculty of Medicine, Tel Aviv University, Israel.
7
Washington University School of Medicine, St. Louis, MO, USA.
8
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
9
The Leeds Teaching Hospitals, St. James Institute of Oncology, UK.
10
Stanford University School of Medicine, CA, USA.
11
Kings College Hospital, NHS Foundation Trust, London, UK.
12
School of Public Health, Silesian Medical University, Katowice, Poland.
13
Royal Bournemouth Hospital, UK.
14
Jiangsu Province Hospital, Nanjing, China.
15
North Shore Hospital, Auckland, New Zealand.
16
Universitair Ziekenhuis Gent, Belgium.
17
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
18
Pharmacyclics, LLC, an AbbVie Company, Sunnyvale, CA, USA.
19
University of California, San Diego, Moores Cancer Center, La Jolla, CA, USA.
20
Università 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 without 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 ibrutinib treatment duration was 28.5 months. Ibrutinib significantly prolonged 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, respectively). 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 substantially from 7% at 12 months to 18% with extended follow up. Greater quality of life improvements occurred with ibrutinib versus chlorambucil in Functional Assessment of Chronic Illness Therapy-Fatigue (P=0.0013). The most frequent grade ≥3 adverse events were neutropenia (12%), anemia (7%), and hypertension (5%). Rate of discontinuations 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 identifier 01722487 and 01724346.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01722487 NCT01724346.

PMID:
29880603
PMCID:
PMC6119145
DOI:
10.3324/haematol.2018.192328
[Indexed for MEDLINE]
Free PMC Article

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