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Targeting of B‐cell receptor signalling in B‐cell malignancies
Author(s) -
Jerkeman M.,
Hallek M.,
Dreyling M.,
Thieblemont C.,
Kimby E.,
Staudt L.
Publication year - 2017
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12600
Subject(s) - ibrutinib , idelalisib , bruton's tyrosine kinase , mantle cell lymphoma , medicine , lenalidomide , chemoimmunotherapy , cancer research , chronic lymphocytic leukemia , follicular lymphoma , tyrosine kinase , lymphoma , b cell receptor , b cell , pharmacology , immunology , leukemia , receptor , multiple myeloma , antibody
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 ( PI 3K), 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 PI 3Kδ 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.