Converging approaches in the frontline treatment of mantle cell lymphoma

Mantle cell lymphoma is a biologically and clinically heterogeneous subtype of non-Hodgkin lymphoma that affects predominantly older patients. The disease remains incurable with modern therapies. The integration of first- and now second-generation Bruton tyrosine kinase inhibitors (BTKis) into earlier-line settings appears to improve outcomes. Remaining questions in the field relate to the need for chemotherapy and the choice and duration of maintenance therapy, given its cost and infectious complications. In this review, we highlight clinical data showing BTKis targeting genetic vulnerabilities within mantle cell lymphoma cells. We then assess the integration of these agents into the first-line setting for all patients with newly diagnosed disease. Special consideration is given to patients with TP53-mutated disease, for which non-chemotherapy approaches are preferred.