PMID- 35377947
OWN - NLM
STAT- MEDLINE
DCOM- 20220610
LR  - 20230109
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 6
IP  - 11
DP  - 2022 Jun 14
TI  - Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for 
      patients with chronic lymphocytic leukemia.
PG  - 3440-3450
LID - 10.1182/bloodadvances.2021006434 [doi]
AB  - We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily 
      Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy 
      with significant progression-free survival (PFS) and overall survival (OS) 
      benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. 
      Patients (>/=65 years) with previously untreated CLL, without del(17p), were 
      randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease 
      progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.8 mg/kg </=12 
      cycles (n = 133). With up to 8 years of follow-up (range, 0.1-96.6 months; 
      median, 82.7 months), significant PFS benefit was sustained for ibrutinib vs 
      chlorambucil (hazard ratio [HR], 0.154; 95% confidence interval [CI], 
      0.108-0.220). At 7 years, PFS was 59% for ibrutinib vs 9% for chlorambucil. PFS 
      benefit was also observed for ibrutinib- vs chlorambucil-randomized patients with 
      high-risk genomic features: del(11q) (HR, 0.033; 95% CI, 0.010-0.107) or 
      unmutated immunoglobulin heavy chain variable region (HR, 0.112; 95% CI, 
      0.065-0.192). OS at 7 years was 78% with ibrutinib. Prevalence of adverse events 
      (AEs) was consistent with previous 5-year follow-up. Ibrutinib dosing was held 
      (>/=7 days) for 79 patients and reduced for 31 patients because of AEs; these AEs 
      resolved or improved in 85% (67 of 79) and 90% (28 of 31) of patients, 
      respectively. With up to 8 years of follow-up, 42% of patients remain on 
      ibrutinib. Long-term RESONATE-2 data demonstrate sustained benefit with 
      first-line ibrutinib treatment for CLL, including for patients with high-risk 
      genomic features. These trials were registered at www.clinicaltrials.gov as 
      #NCT01722487 and #NCT01724346.
CI  - (c) 2022 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Barr, Paul M
AU  - Barr PM
AUID- ORCID: 0000-0002-9733-401X
AD  - Clinical Trials Office, Wilmot  Cancer Institute, University of Rochester Medical 
      Center, Rochester, NY.
FAU - Owen, Carolyn
AU  - Owen C
AD  - Division of Hematology & Hematological Malignancies, Tom Baker Cancer Centre, 
      University of Calgary, Calgary, AB, Canada.
FAU - Robak, Tadeusz
AU  - Robak T
AUID- ORCID: 0000-0002-3411-6357
AD  - Department of Hematology, Medical University of Lodz, Copernicus Memorial 
      Hospital, Lodz, Poland.
FAU - Tedeschi, Alessandra
AU  - Tedeschi A
AD  - Department of Hematology, Azienda Socio Sanitaria Territoriali Grande Ospedale 
      Metropolitano Niguarda, Milan, Italy.
FAU - Bairey, Osnat
AU  - Bairey O
AD  - Department of Hematology, Rabin Medical Center, Petah Tikva, Israel.
FAU - Burger, Jan A
AU  - Burger JA
AUID- ORCID: 0000-0002-6177-7572
AD  - Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, 
      TX.
FAU - Hillmen, Peter
AU  - Hillmen P
AD  - Department of Haematology, The Leeds Teaching Hospitals, St. James Institute of 
      Oncology, Leeds, UK.
FAU - Coutre, Steve E
AU  - Coutre SE
AD  - Hematology Clinic, Stanford Cancer Center, Stanford University School of 
      Medicine, Stanford, CA.
FAU - Dearden, Claire
AU  - Dearden C
AD  - Haemato-Oncology Department, The Royal Marsden Hospital, London, UK.
FAU - Grosicki, Sebastian
AU  - Grosicki S
AD  - Department of Hematology and Cancer Prevention, School of Public Health, Silesian 
      Medical University, Katowice, Poland.
FAU - McCarthy, Helen
AU  - McCarthy H
AD  - Haematology Department, Royal Bournemouth General Hospital, Bournemouth, UK.
FAU - Li, Jian-Yong
AU  - Li JY
AD  - Department of Hematology, Jiangsu Province Hospital, Nanjing, China.
FAU - Offner, Fritz
AU  - Offner F
AD  - Department of Clinical Hematology, Universitair Ziekenhuis Gent, Gent, Belgium.
FAU - Moreno, Carol
AU  - Moreno C
AD  - Department of Hematology, Hospital de la Santa Creu i Sant Pau, Autonomous 
      University of Barcelona, Barcelona, Spain.
FAU - Zhou, Cathy
AU  - Zhou C
AD  - Biostatistics, Pharmacyclics LLC, an AbbVie Company, South San Francisco, CA.
FAU - Hsu, Emily
AU  - Hsu E
AD  - Clinical Sciences, Pharmacyclics LLC, an AbbVie Company, South San Francisco, CA.
FAU - Szoke, Anita
AU  - Szoke A
AD  - Clinical Sciences, Pharmacyclics LLC, an AbbVie Company, South San Francisco, CA.
FAU - Kipps, Thomas J
AU  - Kipps TJ
AUID- ORCID: 0000-0002-0064-4549
AD  - Department of Medicine, University of California San Diego, Moores Cancer Center, 
      San Diego, CA; and.
FAU - Ghia, Paolo
AU  - Ghia P
AUID- ORCID: 0000-0003-3750-7342
AD  - Department of Onco-Hematology, Universita Vita-Salute San Raffaele and Istituto 
      di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, Milan, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT01722487
SI  - ClinicalTrials.gov/NCT01724346
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 18D0SL7309 (Chlorambucil)
RN  - 1X70OSD4VX (ibrutinib)
RN  - JAC85A2161 (Adenine)
SB  - IM
CIN - Future Oncol. 2023 Jan 9;:. PMID: 36617990
MH  - Adenine/analogs & derivatives
MH  - Chlorambucil/adverse effects
MH  - Follow-Up Studies
MH  - Humans
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/genetics
MH  - Piperidines
MH  - Pyrazoles/adverse effects
MH  - Pyrimidines/adverse effects
MH  - Treatment Outcome
PMC - PMC9198904
EDAT- 2022/04/05 06:00
MHDA- 2022/06/11 06:00
PMCR- 2022/06/08
CRDT- 2022/04/04 17:11
PHST- 2021/10/26 00:00 [received]
PHST- 2022/02/28 00:00 [accepted]
PHST- 2022/04/05 06:00 [pubmed]
PHST- 2022/06/11 06:00 [medline]
PHST- 2022/04/04 17:11 [entrez]
PHST- 2022/06/08 00:00 [pmc-release]
AID - 484605 [pii]
AID - 2022/ADV2021006434 [pii]
AID - 10.1182/bloodadvances.2021006434 [doi]
PST - ppublish
SO  - Blood Adv. 2022 Jun 14;6(11):3440-3450. doi: 10.1182/bloodadvances.2021006434.