PMID- 37390310
OWN - NLM
STAT- MEDLINE
DCOM- 20230825
LR  - 20240324
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 142
IP  - 8
DP  - 2023 Aug 24
TI  - Detailed safety profile of acalabrutinib vs ibrutinib in previously treated 
      chronic lymphocytic leukemia in the ELEVATE-RR trial.
PG  - 687-699
LID - 10.1182/blood.2022018818 [doi]
AB  - ELEVATE-RR demonstrated noninferior progression-free survival and lower incidence 
      of key adverse events (AEs) with acalabrutinib vs ibrutinib in previously treated 
      chronic lymphocytic leukemia. We further characterize AEs of acalabrutinib and 
      ibrutinib via post hoc analysis. Overall and exposure-adjusted incidence rate was 
      assessed for common Bruton tyrosine kinase inhibitor-associated AEs and for 
      selected events of clinical interest (ECIs). AE burden scores based on previously 
      published methodology were calculated for AEs overall and selected ECIs. Safety 
      analyses included 529 patients (acalabrutinib, n = 266; ibrutinib, n = 263). 
      Among common AEs, incidences of any-grade diarrhea, arthralgia, urinary tract 
      infection, back pain, muscle spasms, and dyspepsia were higher with ibrutinib, 
      with 1.5- to 4.1-fold higher exposure-adjusted incidence rates. Incidences of 
      headache and cough were higher with acalabrutinib, with 1.6- and 1.2-fold higher 
      exposure-adjusted incidence rate, respectively. Among ECIs, incidences of 
      any-grade atrial fibrillation/flutter, hypertension, and bleeding were higher 
      with ibrutinib, as were exposure-adjusted incidence rates (2.0-, 2.8-, and 
      1.6-fold, respectively); incidences of cardiac events overall (the Medical 
      Dictionary for Regulatory Activities system organ class) and infections were 
      similar between arms. Rate of discontinuation because of AEs was lower for 
      acalabrutinib (hazard ratio, 0.62; 95% confidence interval, 0.41-0.93). AE burden 
      score was higher for ibrutinib vs acalabrutinib overall and for the ECIs atrial 
      fibrillation/flutter, hypertension, and bleeding. A limitation of this analysis 
      is its open-label study design, which may influence the reporting of more 
      subjective AEs. Overall, event-based analyses and AE burden scores demonstrated 
      higher AE burden overall and specifically for atrial fibrillation, hypertension, 
      and hemorrhage with ibrutinib vs acalabrutinib. This trial was registered at 
      www.clinicaltrials.gov as #NCT02477696.
CI  - (c) 2023 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 - Seymour, John F
AU  - Seymour JF
AUID- ORCID: 0000-0003-2188-6835
AD  - Peter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of 
      Melbourne, Melbourne, VIC, Australia.
FAU - Byrd, John C
AU  - Byrd JC
AD  - Department of Internal Medicine, University of Cincinnati College of Medicine, 
      Cincinnati, OH.
FAU - Ghia, Paolo
AU  - Ghia P
AUID- ORCID: 0000-0003-3750-7342
AD  - Division of Experimental Oncology, Universita Vita-Salute San Raffaele and IRCCS 
      Ospedale San Raffaele, Milano, Italy.
FAU - Kater, Arnon P
AU  - Kater AP
AUID- ORCID: 0000-0003-3190-1891
AD  - Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The 
      Netherlands.
FAU - Chanan-Khan, Asher
AU  - Chanan-Khan A
AUID- ORCID: 0000-0002-4702-6772
AD  - Mayo Clinic Jacksonville, Jacksonville, FL.
FAU - Furman, Richard R
AU  - Furman RR
AUID- ORCID: 0000-0003-1677-7626
AD  - Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY.
FAU - O'Brien, Susan
AU  - O'Brien S
AD  - Chao Family Comprehensive Cancer Center, University of California-Irvine, Irvine, 
      CA.
FAU - Brown, Jennifer R
AU  - Brown JR
AUID- ORCID: 0000-0003-2040-4961
AD  - Dana-Farber Cancer Institute, Boston, MA.
FAU - Munir, Talha
AU  - Munir T
AD  - Leeds Teaching Hospital NHS Trust, Leeds, United Kingdom.
FAU - Mato, Anthony
AU  - Mato A
AD  - Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Stilgenbauer, Stephan
AU  - Stilgenbauer S
AUID- ORCID: 0000-0002-6830-9296
AD  - Division of CLL, Department of Internal Medicine III, Ulm University, Ulm, 
      Germany.
FAU - Bajwa, Naghmana
AU  - Bajwa N
AD  - AstraZeneca, Gaithersburg, MD.
FAU - Miranda, Paulo
AU  - Miranda P
AD  - AstraZeneca, Gaithersburg, MD.
FAU - Higgins, Kara
AU  - Higgins K
AD  - AstraZeneca, South San Francisco, CA.
FAU - John, Ellie
AU  - John E
AUID- ORCID: 0000-0002-9234-3275
AD  - AstraZeneca, Cambridge, United Kingdom.
FAU - de Borja, Marianne
AU  - de Borja M
AD  - AstraZeneca, Mississauga, ON, Canada.
FAU - Jurczak, Wojciech
AU  - Jurczak W
AUID- ORCID: 0000-0003-1879-8084
AD  - Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland.
FAU - Woyach, Jennifer A
AU  - Woyach JA
AUID- ORCID: 0000-0002-3403-9144
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, OH.
LA  - eng
SI  - ClinicalTrials.gov/NCT02477696
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - I42748ELQW (acalabrutinib)
RN  - 1X70OSD4VX (ibrutinib)
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
CIN - Blood. 2023 Aug 24;142(8):679-680. PMID: 37616021
CIN - Expert Rev Hematol. 2023 Jul-Dec;16(11):803-806. PMID: 37830359
MH  - Humans
MH  - *Atrial Fibrillation/drug therapy
MH  - Hemorrhage/chemically induced
MH  - *Hypertension/drug therapy
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy
MH  - Protein Kinase Inhibitors/adverse effects
PMC - PMC10644206
COIS- Conflict-of-interest disclosure: J.F.S. serves on the advisory board of AbbVie, 
      AstraZeneca, Celgene, Genentech, Genor Bio, Gilead, Janssen, MorphoSys, Roche, 
      and Sunesis; is a speaker for AbbVie, Celgene, and Roche; reports research 
      funding from AbbVie, Celgene, Janssen, and Roche; provides expert testimony to 
      Celgene, Roche, and TG Therapeutics; and reports consultancy for TG Therapeutics. 
      J.C.B. serves as a consultant for Syndax, Trillium, AstraZeneca, Novartis, 
      Newave, and Kronos; and serves as the scientific advisory board chair of, and is 
      a major stockholder with, Vincerx Pharma. T.M. declares honoraria from 
      AstraZeneca, AbbVie, Janssen, Alexion, Gilead, Roche, and Novartis. P.G. serves 
      as a consultant for AbbVie, AstraZeneca, BeiGene, BMS, Janssen, Lilly/Loxo, MSD, 
      and Roche; and reports research funding from AbbVie, AstraZeneca, BMS, and 
      Janssen. A.P.K. serves as a consultant for AbbVie, AstraZeneca, BeiGene, BMS, 
      Janssen, and Roche/Genentech; and reports research funding from AbbVie, 
      AstraZeneca, BMS, Janssen, and Roche/Genentech. A.C.-K. reports advisory board 
      honoraria, research support, board of director, and trial participation with 
      Ascentage, BeiGene, Cellectar, Starton, Janssen, and Pharmacyclics. R.R.F. serves 
      as a consultant for AbbVie, AstraZeneca, BeiGene, Genentech, Incyte, Janssen, 
      Loxo, MEI Pharma, Pharmacyclics, Sanofi, TG Therapeutics, and X4 Pharmaceuticals. 
      S.O. serves as a consultant for AbbVie, Alexion, Amgen, Aptose Biosciences, 
      Astellas, AstraZeneca, Autolus, BMS, Celgene, DynaMed, Eli Lilly and Company, 
      Gilead, GlaxoSmithKline, Janssen Oncology, Johnson & Johnson, Juno Therapeutics, 
      MEI Pharma Inc, Merck, and NOVA Research; and declares research funding from 
      Acerta, Alliance, BeiGene, Caribou Biosciences, Gilead, Kite, Loxo Oncology, 
      Mustang, Nurix, Pfizer, Pharmacyclics, Regeneron, Sunesis, and TG Therapeutics. 
      J.R.B. serves as a consultant for AbbVie, Acerta/AstraZeneca, BeiGene, Bristol 
      Myers Squibb/Juno/Celgene, Catapult, Eli Lilly, Genentech/Roche, Grifols 
      Worldwide Operations, Hutchmed, iOnctura, Janssen, MEI Pharma, Pfizer, and 
      Pharmacyclics; and declares research funding from BeiGene, Gilead, Loxo/Lilly, 
      MEI Pharma, SecuraBio, Sun, and TG Therapeutics. A.M. serves as a 
      consultant/advisor for AbbVie, Acerta, Adaptive, AstraZeneca, BeiGene, DTRM 
      Biopharma, Genentech, Curio, Dava, Octopharma, Janssen, Johnson & Johnson, Loxo, 
      Nurix, Genmab, BMS, Pharmacyclics, Sunesis, and TG Therapeutics; reports research 
      funding from AbbVie, Octopharma, Acerta, Adaptive, BeiGene, DTRM Biopharma, 
      Genentech, Genmab, Nurix, Janssen, Johnson & Johnson, Loxo, Pharmacyclics, 
      Sunesis, and TG Therapeutics; and reports other relationship(s) with TG 
      Therapeutics (DSMB). S.S. reports receiving advisory board honoraria, research 
      support, travel support, and speaker fees from, and trial participation with 
      AbbVie, AstraZeneca, BeiGene, BMS, Gilead, GSK, Hoffman-La Roche, Janssen, 
      Novartis, Pharmacyclics, and Sunesis. N.B., P.M., K.H., E.J., and M.d.B. reports 
      employment and stock ownership with AstraZeneca. W.J. received research funding 
      from AstraZeneca, Janssen, BeiGene, and Lilly. J.A.W. received research funding 
      from AbbVie, Janssen, Karyopharm, MorphoSys, Pharmacyclics, and Schrodinger; and 
      serves as a consultant for AbbVie, AstraZeneca, BeiGene, Genentech, Janssen, 
      Loxo, Newave, Pharmacyclics, and Schrodinger.
EDAT- 2023/06/30 19:14
MHDA- 2023/08/25 06:42
PMCR- 2023/07/03
CRDT- 2023/06/30 14:23
PHST- 2023/04/23 00:00 [accepted]
PHST- 2022/10/27 00:00 [received]
PHST- 2023/08/25 06:42 [medline]
PHST- 2023/06/30 19:14 [pubmed]
PHST- 2023/06/30 14:23 [entrez]
PHST- 2023/07/03 00:00 [pmc-release]
AID - S0006-4971(23)01551-3 [pii]
AID - 10.1182/blood.2022018818 [doi]
PST - ppublish
SO  - Blood. 2023 Aug 24;142(8):687-699. doi: 10.1182/blood.2022018818.