PMID- 33730844
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20211027
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 106
IP  - 9
DP  - 2021 Sep 1
TI  - Phase II study of acalabrutinib in ibrutinib-intolerant patients with 
      relapsed/refractory chronic lymphocytic leukemia.
PG  - 2364-2373
LID - 10.3324/haematol.2020.272500 [doi]
AB  - B-cell receptor signalling inhibition by targeting Bruton tyrosine kinase (BTK) 
      is effective in treating chronic lymphocytic leukemia (CLL). The BTK inhibitor 
      ibrutinib may be intolerable for some patients. Acalabrutinib is a more selective 
      BTK inhibitor that may be better tolerated by patients who are intolerant to 
      ibrutinib. A phase 2 study of acalabrutinib was conducted in patients with 
      relapsed/refractory CLL who were ibrutinib-intolerant and had continued disease 
      activity. Intolerance was defined as having discontinued ibrutinib due to 
      persistent grade 3/4 adverse events (AEs) or persistent/recurrent grade 2 AEs 
      despite dose modification/interruption. Patients received oral acalabrutinib 100 
      mg twice daily until disease progression or intolerance. Sixty patients were 
      treated. Overall response rate to acalabrutinib was 73% and three patients (5%) 
      achieved complete remission. At median follow-up of 35 months, the median 
      progressionfree and overall survival were not reached; 24-month estimates were 
      72% and 81%, respectively. The most frequent AEs with acalabrutinib were diarrhea 
      (53%), headache (42%), contusion (40%), dizziness (33%), upper respiratory tract 
      infection (33%), and cough (30%). Most common reasons for acalabrutinib 
      discontinuation were progressive disease (23%) and AEs (17%). Most patients with 
      baseline samples (49/52; 94%) and all with on-treatment samples (3/3; 100%) had 
      no detectable BTK and/or PLCG2 mutations. Acalabrutinib is effective and 
      tolerable in most patients with relapsed/refractory CLL who are intolerant of 
      ibrutinib. Acalabrutinib may be useful for patients who may benefit from BTK 
      inhibitor therapy but are ibrutinib intolerant.
FAU - Rogers, Kerry A
AU  - Rogers KA
AD  - The Ohio State University, Columbus, OH. Kerry.Rogers@osumc.edu.
FAU - Thompson, Philip A
AU  - Thompson PA
AD  - MD Anderson Cancer Center, Houston, TX.
FAU - Allan, John N
AU  - Allan JN
AD  - Weill Cornell Medicine, New York, NY.
FAU - Coleman, Morton
AU  - Coleman M
AD  - Weill Cornell Medicine, New York, NY.
FAU - Sharman, Jeff P
AU  - Sharman JP
AD  - Willamette Valley Cancer Institute, Eugene, OR.
FAU - Cheson, Bruce D
AU  - Cheson BD
AD  - Georgetown University Hospital, Washington, DC.
FAU - Jones, Daniel
AU  - Jones D
AD  - The Ohio State University, Columbus, OH.
FAU - Izumi, Raquel
AU  - Izumi R
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Frigault, Melanie M
AU  - Frigault MM
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Quah, Cheng
AU  - Quah C
AD  - Acerta Pharma, South San Francisco, CA.
FAU - Raman, Rakesh K
AU  - Raman RK
AD  - Acerta Pharma, South San Francisco, CA.
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 - Kipps, Thomas J
AU  - Kipps TJ
AD  - UC San Diego Moores Cancer Center, San Diego, CA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02717611
GR  - P30 CA016058/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210901
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Benzamides)
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazines)
RN  - 1X70OSD4VX (ibrutinib)
RN  - I42748ELQW (acalabrutinib)
RN  - JAC85A2161 (Adenine)
SB  - IM
CIN - Haematologica. 2021 Sep 01;106(9):2300-2301. PMID: 33730846
MH  - Adenine/analogs & derivatives
MH  - Benzamides
MH  - Humans
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy
MH  - Piperidines
MH  - Protein Kinase Inhibitors/adverse effects
MH  - Pyrazines
PMC - PMC8409022
EDAT- 2021/03/19 06:00
MHDA- 2021/10/28 06:00
PMCR- 2021/03/18
CRDT- 2021/03/18 04:43
PHST- 2020/09/25 00:00 [received]
PHST- 2021/03/19 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
PHST- 2021/03/18 04:43 [entrez]
PHST- 2021/03/18 00:00 [pmc-release]
AID - 10.3324/haematol.2020.272500 [doi]
PST - epublish
SO  - Haematologica. 2021 Sep 1;106(9):2364-2373. doi: 10.3324/haematol.2020.272500.