Novel agents in the Canadian therapeutic landscape of chronic lymphocytic leukemia

In this brief commentary, we discuss oral novel agents within in the armementarium of therapeutic options for Canadian patients with chronic lymphocytic leukemia (CLL). Previously limited to chemotherapy, the Canadian patient with relapsed or refractory CLL has the option of treatment with B-cell receptor inhibitors ibrutinib or idelalisib (combined with rituximab), both individually showing superiority to anti-CD20 monoclonal antibody comparators regardless of high-risk deletion 17p (del(17p)) status in phase 3 clinical trials. BCL2-inhibitor venetoclax shows impressive efficacy for previously-treated patients with del(17p), but though approved, it is not yet funded. For treatment-naïve patients, ibrutinib has proven superior to chemotherapy for those over 65 with comorbidities, but its role remains to be seen for the young and/or fit. Whereas oral novel agents are generally well-tolerated, some side effects, such as infection, hemorrhage, cardiac arrhythmias and tumour lysis syndrome, can be severe, therefore expert clinical vigilance is essential. Regarding sequencing of these agents, most patients failing ibrutinib or idelalisib do respond to venetoclax. While future studies using combinations of novel agents may eventually obviate the use of chemotherapy for CLL, regimens that can be stopped when minimal residual disease is achieved, such as venetoclax, are particularly relevant for our publicly-funded health care system. For Canadian CLL patients, the availability of oral novel agents has greatly expanded treatment options and is improving outcomes.