Ibrutinib in combination with venetoclax (I+V) in treatment of chronic lymphocytic leukemia

Abstract:

In chronic lymphocytic leukemia the B-receptor signaling pathway, with Bruton‘s tyrosine kinase (BTK), and the regulatory mechanisms of apoptosis with the BCL-2 antiapoptotic protein play a key role. By inhibiting BTK (ibrutinib) and BCL-2 (venetoclax) a synergistic effect is achieved. Treatment with a time-limited, oral combination of ibrutinib and venetoclax (I+V) for 15 months showed significant efficacy in the first line of treatment in patients older than 65 years and in younger patients with comorbidities in comparison to chlorambucil+obinutuzumab, and also in younger and „fit“ patients, with high-risk disease (TP53 abnormalities, complex karyotype) i.e. recruitment was independent of TP53 status. With the arrival of the I+V combination, treatment options for patients with chronic lymphocytic leukemia have significantly improved.

Key words:
BCL-2 anatagonists; BTK inhibitors; chronic lymphocytic leukemia; ibrutinib; venetoclax