BCL-2 and BTK inhibitors for chronic lymphocytic leukemia: current treatments and overcoming resistance

INTRODUCTION: In the last decade, BTK inhibitors and the BCL-2 inhibitor venetoclax have replaced immunochemotherapy in the treatment of CLL. AREAS COVERED: This review describes the use of BTK inhibitors and BCL2 inhibitors in the treatment of naive and relapsed or refractory CLL, with particular attention to the mechanisms of resistance. It also addresses the management of double-refractory patients, and the discovery of novel drugs. The corpus of papers was obtained by a search of the PubMed and Google Scholar databases for articles in English. EXPERT OPINION: Covalent BTK inhibitors and venetoclax are commonly recommended for previously-untreated and relapsed/refractory CLL. However, resistance to both drug classes can develop over time. As such, double-refractory patients are difficult to manage and novel approaches are urgently needed.