PMID- 33907299
OWN - NLM
STAT- MEDLINE
DCOM- 20211230
LR  - 20221018
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 35
IP  - 11
DP  - 2021 Nov
TI  - Pooled analysis of safety data from clinical trials evaluating acalabrutinib 
      monotherapy in mature B-cell malignancies.
PG  - 3201-3211
LID - 10.1038/s41375-021-01252-y [doi]
AB  - Bruton tyrosine kinase (BTK) inhibition is an effective therapy for many B-cell 
      malignancies. Acalabrutinib is a next-generation, potent, highly selective, 
      covalent BTK inhibitor. To characterize acalabrutinib tolerability, we pooled 
      safety data from 1040 patients with mature B-cell malignancies treated with 
      acalabrutinib monotherapy in nine clinical studies (treatment-naive: n = 366 
      [35%], relapsed/refractory: n = 674 [65%]; median [range] age: 67 [32-90] years; 
      median [range] prior treatments: 1 [0-13]; median [range] duration of exposure: 
      24.6 [0.0-58.5] months). The most common adverse events (AEs) were headache 
      (38%), diarrhea (37%), upper respiratory tract infection (22%), contusion (22%), 
      nausea (22%), fatigue (21%), and cough (21%). Serious AEs (SAEs) occurred in 39% 
      of patients; pneumonia (6%) was the only SAE that occurred in >/=2%. Deaths due to 
      AEs occurred in 52 patients (5%); pneumonia (n = 8) was the only fatal AE to 
      occur in >/=3 patients. AEs led to treatment discontinuation in 9%. Rates for the 
      AEs of interest (all grades) included infections (67%), hemorrhages (46%), 
      neutropenia (16%), anemia (14%), second primary malignancies (12%), 
      thrombocytopenia (9%), hypertension (8%), and atrial fibrillation (4%). This 
      pooled analysis confirmed acalabrutinib's tolerability and identified no newly 
      emerging late toxicities, supporting acalabrutinib as a long-term treatment for 
      patients with mature B-cell malignancies.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature Limited.
FAU - Furman, Richard R
AU  - Furman RR
AD  - Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA. 
      rrfurman@med.cornell.edu.
FAU - Byrd, John C
AU  - Byrd JC
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
FAU - Owen, Roger G
AU  - Owen RG
AD  - St. James's University Hospital, Leeds, UK.
FAU - O'Brien, Susan M
AU  - O'Brien SM
AD  - Chao Family Comprehensive Cancer Center, University of California-Irvine, Irvine, 
      CA, USA.
FAU - Brown, Jennifer R
AU  - Brown JR
AUID- ORCID: 0000-0003-2040-4961
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
FAU - Hillmen, Peter
AU  - Hillmen P
AD  - St. James's University Hospital, Leeds, UK.
FAU - Stephens, Deborah M
AU  - Stephens DM
AD  - University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
FAU - Chernyukhin, Nataliya
AU  - Chernyukhin N
AD  - AstraZeneca, South San Francisco, CA, USA.
FAU - Lezhava, Tamara
AU  - Lezhava T
AD  - AstraZeneca, South San Francisco, CA, USA.
FAU - Hamdy, Ahmed M
AU  - Hamdy AM
AD  - AstraZeneca, South San Francisco, CA, USA.
FAU - Izumi, Raquel
AU  - Izumi R
AD  - AstraZeneca, South San Francisco, CA, USA.
FAU - Patel, Priti
AU  - Patel P
AD  - AstraZeneca, South San Francisco, CA, USA.
FAU - Baek, Marshall
AU  - Baek M
AD  - AstraZeneca, South San Francisco, CA, USA.
FAU - Christian, Beth
AU  - Christian B
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
FAU - Dyer, Martin J S
AU  - Dyer MJS
AUID- ORCID: 0000-0002-5033-2236
AD  - The Ernest and Helen Scott Haematological Research Institute, University 
      Hospitals of Leicester NHS Trust, Leicester, UK.
FAU - Streetly, Matthew J
AU  - Streetly MJ
AD  - Guy's Hospital, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
FAU - Sun, Clare
AU  - Sun C
AUID- ORCID: 0000-0001-8498-4729
AD  - National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
FAU - Rule, Simon
AU  - Rule S
AUID- ORCID: 0000-0001-8937-6351
AD  - Plymouth University Medical School, Plymouth, UK.
FAU - Wang, Michael
AU  - Wang M
AUID- ORCID: 0000-0001-9748-5486
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
FAU - Ghia, Paolo
AU  - Ghia P
AUID- ORCID: 0000-0003-3750-7342
AD  - Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, 
      Italy.
FAU - Jurczak, Wojciech
AU  - Jurczak W
AUID- ORCID: 0000-0003-1879-8084
AD  - Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland.
FAU - Pagel, John M
AU  - Pagel JM
AUID- ORCID: 0000-0001-5745-8125
AD  - Swedish Cancer Institute, Seattle, WA, USA.
FAU - Sharman, Jeff P
AU  - Sharman JP
AD  - Willamette Valley Cancer Institute/US Oncology, Eugene, OR, USA.
LA  - eng
GR  - R35 CA198183/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210427
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Pyrazines)
RN  - I42748ELQW (acalabrutinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*adverse effects
MH  - Benzamides/*adverse effects
MH  - Clinical Trials as Topic/*statistics & numerical data
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/etiology/*pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Pyrazines/*adverse effects
MH  - Retrospective Studies
MH  - Survival Rate
MH  - United States/epidemiology
EDAT- 2021/04/29 06:00
MHDA- 2021/12/31 06:00
CRDT- 2021/04/28 06:11
PHST- 2020/09/25 00:00 [received]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/03/19 00:00 [revised]
PHST- 2021/04/29 06:00 [pubmed]
PHST- 2021/12/31 06:00 [medline]
PHST- 2021/04/28 06:11 [entrez]
AID - 10.1038/s41375-021-01252-y [pii]
AID - 10.1038/s41375-021-01252-y [doi]
PST - ppublish
SO  - Leukemia. 2021 Nov;35(11):3201-3211. doi: 10.1038/s41375-021-01252-y. Epub 2021 
      Apr 27.