Universität zu Köln

Jerkeman, M., Hallek, M., Dreyling, M., Thieblemont, C., Kimby, E. and Staudt, L. (2017). Targeting of B-cell receptor signalling in B-cell malignancies. J. Intern. Med., 282 (5). S. 415 - 429. HOBOKEN: WILEY. ISSN 1365-2796

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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 C beta. 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 Waldenstrom's macroglobulinemia; and idelalisib, a PI3K delta 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jerkeman, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreyling, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thieblemont, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kimby, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Staudt, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-212886
DOI:	10.1111/joim.12600
Journal or Publication Title:	J. Intern. Med.
Volume:	282
Number:	5
Page Range:	S. 415 - 429
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2796
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; MARGINAL ZONE LYMPHOMA; SOMATIC MUTATIONS; FOLLICULAR LYMPHOMA; RECURRENT MUTATIONS; CLINICAL IMPACT; GENE-EXPRESSION; CODING GENOME; TUMOR-SUPPRESSOR; NOTCH2 MUTATIONS Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21288