Targeting BTK in CLL: Beyond Ibrutinib.

Article Details

Citation

Bond DA, Woyach JA

Targeting BTK in CLL: Beyond Ibrutinib.

Curr Hematol Malig Rep. 2019 Jun;14(3):197-205. doi: 10.1007/s11899-019-00512-0.

PubMed ID
31028669 [ View in PubMed
]
Abstract

PURPOSE OF REVIEW: While the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL), current limitations include off-target toxicities and the development of resistance. In this review, we summarize the emerging data for alternative BTKi. RECENT FINDINGS: Second-generation BTKi include acalabrutinib, zanubrutinib, and tirabrutinib which offer greater BTK selectivity. While these agents may limit off-target toxicity, they do not overcome common mechanisms of ibrutinib resistance. Reversible BTKi including vecabrutinib and LOXO-305 inhibit BTK in the presence of C481S mutation, and non-selective reversible BTKi, including ARQ-531, may retain activity despite mutations within PLCG2. Early-phase studies are underway to establish the clinical efficacy and toxicity of these agents. A randomized trial of ibrutinib versus acalabrutinib is ongoing, and acalabrutinib may be an option for ibrutinib-intolerant patients. Results from ongoing trials of alternate BTKi will help to define their role in CLL therapy as single agents or in combination therapy.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AcalabrutinibTyrosine-protein kinase BTKProteinHumans
Yes
Inhibitor
Details
IbrutinibTyrosine-protein kinase BTKProteinHumans
Yes
Inhibitor
Details
VecabrutinibTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
ZanubrutinibTyrosine-protein kinase BTKProteinHumans
Yes
Inhibitor
Details