PMID- 33275698
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20231104
IS  - 1520-4383 (Electronic)
IS  - 1520-4391 (Print)
IS  - 1520-4383 (Linking)
VI  - 2020
IP  - 1
DP  - 2020 Dec 4
TI  - Managing toxicities of Bruton tyrosine kinase inhibitors.
PG  - 336-345
LID - 10.1182/hematology.2020000118 [doi]
AB  - Inhibition of Bruton's tyrosine kinase (BTK) has revolutionized the treatment 
      landscape for patients with chronic lymphocytic leukemia (CLL). By targeting this 
      critical kinase in proximal B-cell receptor signaling, BTK inhibitors (BTKis) 
      impair cell proliferation, migration, and activation of NF-kappaB. Clinically, 
      because indefinite inhibition is a mainstay of therapy, there is an extended 
      period of exposure in which adverse effects can develop. Given the impressive 
      efficacy and activity of BTKis in the treatment of patients with CLL, appropriate 
      management of treatment-emergent adverse events (AEs) is of paramount importance. 
      Here we review the BTKi landscape and present the available toxicity and safety 
      data for each agent. The long-term toxicity profile of ibrutinib, a 
      first-in-class inhibitor, is well characterized and includes a clinically 
      significant incidence of cardiac arrhythmias, bleeding, infection, diarrhea, 
      arthralgias, and hypertension. Acalabrutinib, the initial second-generation BTKi 
      to earn approval from the US Food and Drug Administration, demonstrates improved 
      kinase selectivity for BTK, with commonly observed adverse reactions including 
      infection, headache, and diarrhea. Mediated by both on-target inhibition of BTK 
      and variable off-target inhibition of other kinases including 
      interleukin-2-inducible T-cell kinase (ITK), tyrosine-protein kinase (TEC), and 
      endothelial growth factor receptor (EGFR), the toxicity profile of BTKis is 
      closely linked to their pattern of kinase binding. Other emerging BTKis include 
      second-generation agents with variable degrees of kinase selectivity and 
      third-generation agents that exhibit reversible noncovalent binding to BTK. We 
      also highlight critical considerations for the prevention and monitoring of AEs 
      and offer practical management strategies for treatment-emergent toxicities.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Lipsky, Andrew
AU  - Lipsky A
AD  - Columbia University Medical Center, New York, NY.
FAU - Lamanna, Nicole
AU  - Lamanna N
AD  - Columbia University Medical Center, New York, NY.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Hematology Am Soc Hematol Educ Program
JT  - Hematology. American Society of Hematology. Education Program
JID - 100890099
RN  - 0 (Benzamides)
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazines)
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/adverse effects/analogs & derivatives/toxicity
MH  - Agammaglobulinaemia Tyrosine Kinase/*antagonists & inhibitors
MH  - Aged
MH  - Animals
MH  - Arrhythmias, Cardiac/chemically induced/therapy
MH  - Arthralgia/chemically induced/therapy
MH  - Benzamides/adverse effects/toxicity
MH  - Diarrhea/chemically induced/therapy
MH  - Hemorrhage/chemically induced/therapy
MH  - Humans
MH  - Hypertension/chemically induced/therapy
MH  - Infection Control
MH  - Infections/chemically induced
MH  - Male
MH  - Piperidines/adverse effects/toxicity
MH  - Protein Kinase Inhibitors/*adverse effects/toxicity
MH  - Pyrazines/adverse effects/toxicity
PMC - PMC7727553
COIS- Conflict-of-interest disclosure: A. L. has no conflicts to disclose. N. L. is on 
      advisory board committees at: Abbvie, AstraZeneca, Bei-Gene, Juno, Loxo, 
      Oncternal, Mingsight, and TG Therapeutics. Additionally, N. L. provides research 
      support to the following institutions: Abbvie, AstraZeneca, Bei-Gene, Celgene, 
      Genentech, Janssen, Pharmacyclics, and Verastem.
EDAT- 2020/12/05 06:00
MHDA- 2021/05/11 06:00
PMCR- 2020/12/04
CRDT- 2020/12/04 17:10
PHST- 2020/12/04 17:10 [entrez]
PHST- 2020/12/05 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2020/12/04 00:00 [pmc-release]
AID - 474309 [pii]
AID - 2020000118C [pii]
AID - 10.1182/hematology.2020000118 [doi]
PST - ppublish
SO  - Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):336-345. doi: 
      10.1182/hematology.2020000118.