Inhibition of Bruton’s tyrosine kinase (BTK) is a well-established therapeutic approach in B-cell malignancies and two BTK inhibitors, ibrutinib and acalabrutinib, have been approved by the U.S. Food and Drug Administration (FDA). In this new work by Bertoni’s lab and published on Haematologica, Chiara Tarantelli and colleagues studied an investigational second generation irreversible BTK inhibitor, zanubrutinib (BGB-3111), in combination with other targeted agents in lymphoma models. Zanubrutinib showed synergism when combined with the BET bromodomain inhibitor birabresib, the XPO1 antagonist selinexor, and especially with the MEK inhibitor pimasertib or the BCL2 inhibitor venetoclax. Interestingly, we also provide data showing a different anti-tumor activity between 1st and 2nd generation BTK inhibitors.
The second Author, Lu Zhang, was a recipient of a fellowship from the European School of Oncology and by a grant from the National Nature Science Foundation of China (No.81400172).
The BTK inhibitor zanubrutinib (BGB-3111) demonstrated synergies with other anti-lymphoma targeted agents
Chiara Tarantelli, Lu Zhang, Elisabetta Curti, Eugenio Gaudio, Filippo Spriano, Valdemar Priebe, Luciano Cascione, Alberto J. Arribas, Emanuele Zucca, Davide Rossi, Anastasios Stathis, Francesco Bertoni
Haematologica January 2019 : haematol.2018.214759; Doi:10.3324/haematol.2018.214759