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Targeting of B-cell receptor signalling in B-cell malignancies

Jerkeman, M. LU ; Hallek, M; Dreyling, M; Thieblemont, Catherine; Kimby, E and Staudt, L. (2017) In Journal of Internal Medicine1989-01-01+01:00 282(5). p.415-428
Abstract

Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B-cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with... (More)

Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B-cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with chemotherapy. In CLL, both ibrutinib and idelalisib have an established role as first-line therapy in patients with del(17p), and in MCL, ibrutinib is a standard option for patients relapsing after chemoimmunotherapy. Unexpected toxicities have been encountered when combining these potent new agents with other drugs, including chemotherapy and lenalidomide, and based on this experience the risks and benefits of novel combinations must be evaluated carefully. In this review, we summarize the efficacy and safety results with these inhibitors and discuss novel combinations that are under study and the future role of BCR inhibitors in these disorders.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
B-cell receptor, Leukaemia, Lymphoma
in
Journal of Internal Medicine1989-01-01+01:00
volume
282
issue
5
pages
415 - 428
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • scopus:85015345103
  • wos:000413307000005
ISSN
0954-6820
DOI
10.1111/joim.12600
language
English
LU publication?
yes
id
5b394476-ab57-4c9f-93b2-fa22354010ce
date added to LUP
2017-04-07 11:34:30
date last changed
2018-10-31 18:21:49
@article{5b394476-ab57-4c9f-93b2-fa22354010ce,
  abstract     = {<p>Pharmacological agents that inhibit enzymes of the B-cell receptor (BCR) pathway are of increasing importance in the treatment of B-cell malignancies. These include inhibitors of Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), splenic tyrosine kinase and protein kinase Cβ. Two agents are already approved in the USA and Europe: ibrutinib, a BTK inhibitor, for the treatment of chronic lymphatic leukaemia (CLL), mantle cell lymphoma (MCL) and Waldenström's macroglobulinemia; and idelalisib, a PI3Kδ inhibitor, for the treatment of CLL and follicular lymphoma. In addition, the role of these drugs in diffuse large B-cell lymphoma and marginal zone lymphoma is under investigation, as single agents and in combination with chemotherapy. In CLL, both ibrutinib and idelalisib have an established role as first-line therapy in patients with del(17p), and in MCL, ibrutinib is a standard option for patients relapsing after chemoimmunotherapy. Unexpected toxicities have been encountered when combining these potent new agents with other drugs, including chemotherapy and lenalidomide, and based on this experience the risks and benefits of novel combinations must be evaluated carefully. In this review, we summarize the efficacy and safety results with these inhibitors and discuss novel combinations that are under study and the future role of BCR inhibitors in these disorders.</p>},
  author       = {Jerkeman, M. and Hallek, M and Dreyling, M and Thieblemont, Catherine and Kimby, E and Staudt, L.},
  issn         = {0954-6820},
  keyword      = {B-cell receptor,Leukaemia,Lymphoma},
  language     = {eng},
  number       = {5},
  pages        = {415--428},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine1989-01-01+01:00},
  title        = {Targeting of B-cell receptor signalling in B-cell malignancies},
  url          = {http://dx.doi.org/10.1111/joim.12600},
  volume       = {282},
  year         = {2017},
}