PMID- 33786588
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20240207
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 137
IP  - 24
DP  - 2021 Jun 17
TI  - Acalabrutinib in treatment-naive chronic lymphocytic leukemia.
PG  - 3327-3338
LID - 10.1182/blood.2020009617 [doi]
AB  - Acalabrutinib has demonstrated significant efficacy and safety in relapsed 
      chronic lymphocytic leukemia (CLL). Efficacy and safety of acalabrutinib 
      monotherapy were evaluated in a treatment-naive CLL cohort of a single-arm phase 
      1/2 trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was 
      declined or deemed inappropriate due to comorbidities (N = 99). Patients had a 
      median age of 64 years and 47% had Rai stage III/IV disease. Acalabrutinib was 
      administered orally 200 mg once daily, or 100 mg twice daily until progression or 
      intolerance. A total of 99 patients were treated; 57 (62%) had unmutated 
      immunoglobulin heavy-chain variable gene, and 12 (18%) had TP53 aberrations. 
      After median follow-up of 53 months, 85 patients remain on treatment; 14 
      discontinued treatment, mostly because of adverse events (AEs) (n = 6) or disease 
      progression (n = 3). Overall response rate was 97% (90% partial response; 7% 
      complete response), with similar outcomes among all prognostic subgroups. Because 
      of improved trough BTK occupancy with twice-daily dosing, all patients were 
      transitioned to 100 mg twice daily. Median duration of response (DOR) was not 
      reached; 48-month DOR rate was 97% (95% confidence interval, 90-99). Serious AEs 
      were reported in 38 patients (38%). AEs required discontinuation in 6 patients 
      (6%) because of second primary cancers (n = 4) and infection (n = 2). Grade >/=3 
      events of special interest included infection (15%), hypertension (11%), bleeding 
      events (3%), and atrial fibrillation (2%). Durable efficacy and long-term safety 
      of acalabrutinib in this trial support its use in clinical management of 
      symptomatic, untreated patients with CLL.
CI  - (c) 2021 by The American Society of Hematology.
FAU - Byrd, John C
AU  - Byrd JC
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, OH.
FAU - Woyach, Jennifer A
AU  - Woyach JA
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, OH.
FAU - Furman, Richard R
AU  - Furman RR
AD  - Division of Hematology and Oncology, Weill Cornell Medical College, New York 
      Presbyterian Hospital, New York, NY.
FAU - Martin, Peter
AU  - Martin P
AD  - Division of Hematology and Oncology, Weill Cornell Medical College, 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
AD  - Dana-Farber Cancer Institute, Boston, MA.
FAU - Stephens, Deborah M
AU  - Stephens DM
AUID- ORCID: 0000-0001-9188-5008
AD  - University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
FAU - Barrientos, Jacqueline C
AU  - Barrientos JC
AD  - Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY.
FAU - Devereux, Stephen
AU  - Devereux S
AD  - College Hospital, NHS Foundation Trust Denmark Hill, London, United Kingdom.
FAU - Hillmen, Peter
AU  - Hillmen P
AUID- ORCID: 0000-0001-5617-4403
AD  - St James's University Hospital, Leeds, United Kingdom.
FAU - Pagel, John M
AU  - Pagel JM
AD  - Swedish Cancer Institute, Seattle, WA.
FAU - Hamdy, Ahmed
AU  - Hamdy A
AD  - AstraZeneca, South San Francisco, CA; and.
FAU - Izumi, Raquel
AU  - Izumi R
AD  - AstraZeneca, South San Francisco, CA; and.
FAU - Patel, Priti
AU  - Patel P
AD  - AstraZeneca, South San Francisco, CA; and.
FAU - Wang, Min Hui
AU  - Wang MH
AD  - AstraZeneca, South San Francisco, CA; and.
FAU - Jain, Nitin
AU  - Jain N
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, TX.
FAU - Wierda, William G
AU  - Wierda WG
AD  - Department of Leukemia, The University of Texas MD Anderson Cancer Center, 
      Houston, TX.
LA  - eng
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - R35 CA197734/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
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
JT  - Blood
JID - 7603509
RN  - 0 (Benzamides)
RN  - 0 (Pyrazines)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - I42748ELQW (acalabrutinib)
SB  - IM
CIN - Blood. 2021 Jun 17;137(24):3313-3314. PMID: 34137848
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Benzamides/administration & dosage/adverse effects/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug 
      therapy/genetics/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm Staging
MH  - *Pyrazines/administration & dosage/adverse effects/pharmacokinetics
MH  - Tumor Suppressor Protein p53/genetics
PMC - PMC8670015
EDAT- 2021/04/01 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/06/17
CRDT- 2021/03/31 06:46
PHST- 2020/10/28 00:00 [received]
PHST- 2021/02/20 00:00 [accepted]
PHST- 2021/04/01 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/03/31 06:46 [entrez]
PHST- 2021/06/17 00:00 [pmc-release]
AID - S0006-4971(21)00755-2 [pii]
AID - 2021/BLD2020009617 [pii]
AID - 10.1182/blood.2020009617 [doi]
PST - ppublish
SO  - Blood. 2021 Jun 17;137(24):3327-3338. doi: 10.1182/blood.2020009617.