Report of Consensus Panel 5 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with intolerance or resistance to covalent BTK inhibitors

Abstract

Over the last decade, covalent Bruton tyrosine kinase (BTK) inhibitors have become a standard option for treating patients with symptomatic Waldenström Macroglobulinemia (WM) in the frontline or relapsed settings. However, the definition of intolerance and resistance to covalent BTK inhibitors has not been established. Understanding the best approaches to managing such patients is crucial to avoiding premature abandonment of effective therapy or pursuing futile therapies unlikely to be effective in controlling symptomatic disease progression. With the advent of noncovalent BTK inhibitors and BCL2 antagonists, in addition to clinical trials evaluating phospholipid-drug conjugates, antibody-drug conjugates, and bispecific antibodies, the present Consensus Panel 5 aims to establish working definitions for intolerance and resistance to covalent BTK inhibitors, as well as provide strategies to identify and manage these issues not infrequently encountered in clinical practice.

Keywords: Covalent BTK inhibitors; Intolerance; Pirtobrutinib; Resistance; Venetoclax; Waldenstrom Macroglobulinemia.