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Abstract
The understanding of the B cell receptor (BCR) pathway and its contribution to chronic lymphocytic leukemia (CLL) pathogenesis have led to the development of targeted BCR inhibitors which have transformed the treatment paradigm of CLL. Ibrutinib is a first-in-class oral Bruton’s tyrosine kinase (BTK) inhibitor which has demonstrated improvements in both progression free (PFS) and overall survival (OS) in both the treatment naïve and relapsed/refractory setting as compared to traditional chemoimmunotherapy. Despite its clinical efficacy, many patients discontinue treatment due to adverse events, which are thought to be mediated through off-target kinase inhibition. Zanubrutinib is a second-generation non-covalent BTK inhibitor with higher potency, allowing for inhibition of BTK with fewer off target effects. Early phase clinical trials have demonstrated excellent efficacy and a well-tolerated safety profile. Long-term follow-up is needed, but zanubrutinib holds promise to be an effective therapy for CLL with a manageable side effect profile and will be an exciting addition to our treatment paradigm.
Disclosure
Dr Joanna M Rhodes reports grants from Conquer Cancer Foundation, during the conduct of the study; personal fees from Pharmacyclics, AstraZeneca, Verastem, and Abbvie/Genentech, outside the submitted work. Dr Anthony R Mato reports grants and/or personal fees from TG Therapeutics, Loxo, Sunesis, Genentech, Abbvie, J and J, Pharmacyclics, DTRM, Octopharma, Aprea, Genmab, Nurix, and Beigene, during the conduct of the study; grants, personal fees from LOXO, TG Therapeutics, AZ, PCYC, J and J, Sunesis, DTRM, Genentech, Nurix, and Genmab, outside the submitted work. The authors report no other conflicts of interest in this work.