Advances in non-cytotoxic treatment of chronic lymphocytic leukaemia: Ibrutinib

Chronic lymphocytic leukaemia is the most common lymphoproliferative disorder among adults in the Western hemisphere. The heterogeneous aetiology, clinical presentation and underlying genetic profile among patients accounts for the variable responses to the gold-standard treatment regimens, namely single-agent or combination chemo-immunotherapy. Recent focussing on the B-cell receptor (BCR) signalling cascade as a central player in the development and maintenance of chronic lymphocytic leukaemia opened new horizons for targeted therapy. Selective inhibition of the Bruton tyrosine kinase (BTK) in the downstream pathway by ibrutinib, the first BTK inhibitor to enter clinical trials, has shown astounding and promising results; when used as a single agent or implemented into combination chemotherapy, ibrutinib displayed impressive clinical efficacy and safety in CLL, including cases featuring poor prognostic factors and relapsed or refractory disease. The exclusive low-toxicity profile, lack of the typical cytotoxic therapy-associated complications (particularly myelosuppression), high-tolerability across different disease groups and encouraging response rates even in high-risk disease categories have contributed to the growing excitement around this potent and irreversible kinase inhibitor. Ibrutinib’s unique biochemistry, pharmacodynamic and pharmacokinetic features and remarkable activity earned it the nomination of breakthrough therapy for CLL by the Food and Drug Association in 2012 and its early approval for treatment in 2013. This frontier agent has also showed its worth in numerous other lymphocytic tumour clinical trials, including mantle cell lymphoma and multiple myeloma, and proved itself as an extremely valuable ally for patient-tailored combination therapy. The objective of this work is to illustrate how the introduction of ibrutinib into the therapeutic script marks the beginning of an exciting era for the treatment of lymphoproliferative malignancies.egységes, osztatlanáltalános orvosango