During the past 10 years, BTK inhibitors are increasingly replacing chemotherapy-based regimens, especially in patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Current clinical practice is continuous long-term administration of covalent, irreversible BTK inhibitors, which can be complicated by side effects or the development of drug resistance. Resistance mutations and intolerance contribute to therapy interruption or discontinuation and abrogate clinical benefits associated with continued covalent BTK inhibitor therapy, leading to subsequent care that is suboptimal due to a dearth of effective treatment options (as reflected in lower progression-free survival, overall survival, or response duration). Non-covalent, reversible BTK inhibitors do not bind to C481, therefore providing a potentially effective option to patients with B cell malignancies that have developed resistance to covalent BTK inhibitors. Preliminary clinical studies have suggested that non-covalent BTK inhibitors are effective and well-tolerated.
This educational activity will assist hematology-oncology professionals develop management plans designed to overcome these challenges and offer patients the full benefit of BTK inhibitor therapy. We will discuss the clinical implications of BTK inhibitor selectivity profiles and safety differences; the integration of BTK inhibitors into the management of different B-cell cancer patient populations; and the proactive adaptation of treatment plans to account for drug resistance and therapeutic intolerance associated with covalent BTK agents.