PMID- 30061088
OWN - NLM
STAT- MEDLINE
DCOM- 20191021
LR  - 20211204
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 18
IP  - 10
DP  - 2018 Oct
TI  - Safety Analysis of Four Randomized Controlled Studies of Ibrutinib in Patients 
      With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Mantle Cell 
      Lymphoma.
PG  - 648-657.e15
LID - S2152-2650(18)30265-9 [pii]
LID - 10.1016/j.clml.2018.06.016 [doi]
AB  - BACKGROUND: Multiple studies have demonstrated the efficacy and safety of 
      ibrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) 
      and mantle cell lymphoma (MCL). This first-in-class inhibitor of Bruton's 
      tyrosine kinase has become a standard treatment for patients with CLL and MCL. 
      PATIENTS AND METHODS: We conducted an integrated safety analysis to characterize 
      the frequency, severity, natural history, and outcomes of adverse events (AEs) 
      with ibrutinib versus comparators. Data were pooled from 4 completed randomized 
      controlled studies that had included 756 ibrutinib-treated and 749 
      comparator-treated patients with CLL/SLL or relapsed/refractory MCL. Safety 
      analyses included reporting of AEs using crude and exposure-adjusted incidence 
      rates. RESULTS: The median treatment duration was 13.3 months (maximum, 28.2 
      months) for ibrutinib and 5.8 months (maximum, 27.3 months) for comparators. When 
      adjusted for exposure, diarrhea, atrial fibrillation, and hypertension were the 
      only common grade >/= 3 AEs more often reported with ibrutinib than with the 
      comparators. Dose reductions (7% vs. 14%) and discontinuation (12% vs. 16%) 
      because of AEs occurred less often with ibrutinib, and deaths due to AEs occurred 
      at similar rates (6% vs. 7%). When adjusted for exposure, the corresponding data 
      were all lower with ibrutinib than with the comparators (0.06 vs. 0.22, 0.11 vs. 
      0.22, and 0.06 vs. 0.09 patient-exposure-years, respectively). The prevalence of 
      common grade 3/4 AEs with ibrutinib generally decreased over time, with the 
      exception of hypertension. CONCLUSION: These results from an integrated analysis 
      support a favorable benefit/risk profile of ibrutinib in patients with CLL/SLL 
      and MCL.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - O'Brien, Susan
AU  - O'Brien S
AD  - Chao Family Comprehensive Cancer Center, University of California, Irvine, 
      Orange, CA. Electronic address: obrien@uci.edu.
FAU - Hillmen, Peter
AU  - Hillmen P
AD  - The Leeds Teaching Hospitals, St. James University Hospital, Leeds, United 
      Kingdom.
FAU - Coutre, Steven
AU  - Coutre S
AD  - Stanford University School of Medicine, Stanford, CA.
FAU - Barr, Paul M
AU  - Barr PM
AD  - Wilmot Cancer Institute, University of Rochester Cancer Center, Rochester, NY.
FAU - Fraser, Graeme
AU  - Fraser G
AD  - Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
FAU - Tedeschi, Alessandra
AU  - Tedeschi A
AD  - ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
FAU - Burger, Jan A
AU  - Burger JA
AD  - University of Texas MD Anderson Cancer Center, Houston, TX.
FAU - Dilhuydy, Marie-Sarah
AU  - Dilhuydy MS
AD  - Centre Hospitalier Universitaire Hopitaux de Bordeaux, Pessac, France.
FAU - Hess, Georg
AU  - Hess G
AD  - Universitats Medizin Mainz, Mainz, Germany.
FAU - Moreno, Carol
AU  - Moreno C
AD  - Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
FAU - Cramer, Paula
AU  - Cramer P
AD  - University of Cologne, German CLL Study Group, Cologne, Germany.
FAU - Liu, Emily
AU  - Liu E
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Chang, Stephen
AU  - Chang S
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Vermeulen, Jessica
AU  - Vermeulen J
AD  - Janssen Research & Development, Leiden, The Netherlands.
FAU - Styles, Lori
AU  - Styles L
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Howes, Angela
AU  - Howes A
AD  - Janssen Research & Development, Raritan, NJ.
FAU - James, Danelle F
AU  - James DF
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Patel, Kalpesh
AU  - Patel K
AD  - Janssen Pharmaceuticals, Inc, Titusville, NJ.
FAU - Graef, Thorsten
AU  - Graef T
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
FAU - Valentino, Rudolph
AU  - Valentino R
AD  - Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180628
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 18D0SL7309 (Chlorambucil)
RN  - 1X70OSD4VX (ibrutinib)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 624KN6GM2T (temsirolimus)
RN  - JAC85A2161 (Adenine)
RN  - M95KG522R0 (ofatumumab)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenine/analogs & derivatives
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Chlorambucil/administration & dosage
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/pathology
MH  - Lymphoma, Mantle-Cell/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - *Patient Safety
MH  - Piperidines
MH  - Prognosis
MH  - Pyrazoles/administration & dosage
MH  - Pyrimidines/administration & dosage
MH  - Rituximab/administration & dosage
MH  - Sirolimus/administration & dosage/analogs & derivatives
MH  - Survival Rate
OTO - NOTNLM
OT  - Adverse events
OT  - Benefit/risk profile
OT  - Bruton's tyrosine kinase inhibitor
OT  - Exposure-adjusted incidence rate
OT  - Pooled analysis
EDAT- 2018/08/01 06:00
MHDA- 2019/10/23 06:00
CRDT- 2018/08/01 06:00
PHST- 2018/03/14 00:00 [received]
PHST- 2018/06/16 00:00 [revised]
PHST- 2018/06/19 00:00 [accepted]
PHST- 2018/08/01 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/08/01 06:00 [entrez]
AID - S2152-2650(18)30265-9 [pii]
AID - 10.1016/j.clml.2018.06.016 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2018 Oct;18(10):648-657.e15. doi: 
      10.1016/j.clml.2018.06.016. Epub 2018 Jun 28.