PMID- 31088809
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20211204
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 3
IP  - 9
DP  - 2019 May 14
TI  - Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are 
      intolerant to ibrutinib.
PG  - 1553-1562
LID - 10.1182/bloodadvances.2018030007 [doi]
AB  - The Bruton tyrosine kinase (BTK) inhibitor ibrutinib improves patient outcomes in 
      chronic lymphocytic leukemia (CLL); however, some patients experience adverse 
      events (AEs) leading to discontinuation. Acalabrutinib is a potent, covalent BTK 
      inhibitor with greater selectivity than ibrutinib. We evaluated the safety and 
      efficacy of 100 mg of acalabrutinib twice daily or 200 mg once daily in patients 
      with CLL who discontinued ibrutinib because of intolerance as determined by the 
      investigators. Among 33 treated patients (61% men; median age, 64 years; range, 
      50-82 years), median duration of prior ibrutinib treatment was 11.6 months 
      (range, 1-62 months); median time from ibrutinib discontinuation to acalabrutinib 
      start was 47 days (range, 3-331 days). After a median of 19.0 months (range, 
      0.2-30.6 months), 23 patients remained on acalabrutinib; 10 had discontinued 
      (progressive disease, n = 4; AEs, n = 3). No acalabrutinib dose reductions 
      occurred. During acalabrutinib treatment, the most frequent AEs included diarrhea 
      (58%), headache (39%), and cough (33%). Grade 3/4 AEs occurred in 58%, most 
      commonly neutropenia (12%) and thrombocytopenia (9%). Of 61 ibrutinib-related AEs 
      associated with intolerance, 72% did not recur and 13% recurred at a lower grade 
      with acalabrutinib. Overall response rate was 76%, including 1 complete and 19 
      partial responses and 5 partial responses with lymphocytosis. Among 25 
      responders, median duration of response was not reached. Median progression-free 
      survival (PFS) was not reached; 1-year PFS was 83.4% (95% confidence interval, 
      64.5%-92.7%). Acalabrutinib was well tolerated with a high response rate in 
      patients who were previously intolerant to ibrutinib. This trial was registered 
      at www.clinicaltrials.gov as #NCT02029443.
CI  - (c) 2019 by The American Society of Hematology.
FAU - Awan, Farrukh T
AU  - Awan FT
AUID- ORCID: 0000-0003-1813-9812
AD  - Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern 
      Medical Center, Dallas, TX.
FAU - Schuh, Anna
AU  - Schuh A
AD  - Department of Haematology, Oxford University Hospitals NHS Foundation Trust, 
      Oxford, United Kingdom.
FAU - Brown, Jennifer R
AU  - Brown JR
AD  - Dana-Farber Cancer Institute, Boston, MA.
FAU - Furman, Richard R
AU  - Furman RR
AD  - New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY.
FAU - Pagel, John M
AU  - Pagel JM
AD  - Swedish Cancer Institute, Seattle, WA.
FAU - Hillmen, Peter
AU  - Hillmen P
AUID- ORCID: 0000-0001-5617-4403
AD  - St. James's University Hospital, Leeds, United Kingdom.
FAU - Stephens, Deborah M
AU  - Stephens DM
AUID- ORCID: 0000-0001-9188-5008
AD  - Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
FAU - Woyach, Jennifer
AU  - Woyach J
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, OH.
FAU - Bibikova, Elena
AU  - Bibikova E
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Charuworn, Prista
AU  - Charuworn P
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Frigault, Melanie M
AU  - Frigault MM
AD  - Acerta Pharma, South San Francisco, CA.
AD  - Oncology Translational Science, and.
FAU - Hamdy, Ahmed
AU  - Hamdy A
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Izumi, Raquel
AU  - Izumi R
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Linghu, Bolan
AU  - Linghu B
AD  - Oncology Biosciences, IMED Biotech Unit, AstraZeneca, Boston, MA.
FAU - Patel, Priti
AU  - Patel P
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Wang, Min Hui
AU  - Wang MH
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Byrd, John C
AU  - Byrd JC
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, OH.
LA  - eng
SI  - ClinicalTrials.gov/NCT02029443
GR  - R35 CA197734/CA/NCI NIH HHS/United States
GR  - R01 CA177292/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazines)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - 1X70OSD4VX (ibrutinib)
RN  - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
RN  - EC 2.7.10.2 (BTK protein, human)
RN  - I42748ELQW (acalabrutinib)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/analogs & derivatives
MH  - Agammaglobulinaemia Tyrosine Kinase/metabolism
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/metabolism/*therapeutic use
MH  - Benzamides/adverse effects/metabolism/*therapeutic use
MH  - Diarrhea/etiology
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Phosphorylation
MH  - Piperidines
MH  - Progression-Free Survival
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Pyrazines/adverse effects/metabolism/*therapeutic use
MH  - Pyrazoles/therapeutic use
MH  - Pyrimidines/therapeutic use
MH  - Treatment Outcome
PMC - PMC6517672
COIS- Conflict-of-interest disclosure: F.T.A. has been a consultant for AbbVie, 
      Janssen, Gilead, Sunesis, AstraZeneca, Genentech, and Pharmacyclics, received 
      research funding from Innate Pharma and Pharmacyclics, and served on speakers' 
      bureaus for AstraZeneca and AbbVie. A.S. has been a consultant for and has 
      received honoraria from AbbVie, Gilead, GlaxoSmithKline, Janssen, Novartis, and 
      Roche. J.R.B. has been a consultant for AbbVie, Astellas Pharma, AstraZeneca, 
      Celgene, Gilead, Verastem Pharmaceuticals, Janssen, Pfizer, Pharmacyclics, Redx, 
      Roche/Genentech, and Sun BioPharma. R.R.F. has been a consultant for AbbVie, 
      Acerta Pharma, Genentech, Gilead, Incyte, Janssen, Loxo Oncology, Pharmacyclics, 
      Sunesis, TG Therapeutics, and Verastem. J.M.P. has been a consultant for Gilead 
      and Pharmacyclics and has equity ownership in and received research funding from 
      Actinium Pharmaceuticals. P.H. has been a consultant for AbbVie, Acerta Pharma, 
      Alexion Pharmaceuticals, Gilead, and Janssen, has received honoraria from AbbVie, 
      Acerta Pharma, Alexion Pharmaceuticals, Gilead, and Janssen, and has received 
      research funding from AbbVie, Gilead, Janssen, GlaxoSmithKline, Pharmacyclics, 
      and Roche. D.M.S. has received research funding from the Lymphoma Research 
      Foundation. J.W. has been a consultant for Janssen and received research funding 
      from Acerta, AbbVie, Karyopharm, and Morphosys. P.C. is an employee of Acerta 
      Pharma. M.M.F. is an employee of and holds stock in AstraZeneca. B.L. is an 
      employee of AstraZeneca. A.H. and R.I. are patent holders and employees of Acerta 
      Pharma and have equity ownership. E.B., M.H.W., and P.P. are employees of Acerta 
      Pharma and have equity ownership. J.C.B. has received research funding from 
      Acerta Pharma, Genentech, Janssen, and Pharmacyclics.
EDAT- 2019/05/16 06:00
MHDA- 2020/05/12 06:00
PMCR- 2019/05/14
CRDT- 2019/05/16 06:00
PHST- 2018/12/14 00:00 [received]
PHST- 2019/03/08 00:00 [accepted]
PHST- 2019/05/16 06:00 [entrez]
PHST- 2019/05/16 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2019/05/14 00:00 [pmc-release]
AID - bloodadvances.2018030007 [pii]
AID - 2018/030007 [pii]
AID - 10.1182/bloodadvances.2018030007 [doi]
PST - ppublish
SO  - Blood Adv. 2019 May 14;3(9):1553-1562. doi: 10.1182/bloodadvances.2018030007.