"The End of the Golden Weather": therapeutic strategies for mantle cell lymphoma relapsed or refractory to covalent BTK inhibitors.

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma, often characterized by a pattern of continued relapse after front-line chemoimmunotherapy. Although patients are usually able to regain durable disease control with covalent Bruton's tyrosine kinase inhibitors (cBTKi) at first relapse, it is now appreciated that such responses are often not sustained and the management of such patients represents a significant area of unmet need. There is an imperative to better understand resistance mechanisms and identify high-risk subsets of patients for whom cBTKi responses may be particularly short. Allogeneic stem cell transplant has an established role in appropriate candidates; however, contemporary consensus is to preferentially offer chimeric antigen receptor (CAR) T-cell therapy. In this Review, we consider the available data on both existing and emerging treatment options, including non-covalent BTK inhibitors, bispecific antibodies, antibody-drug conjugates and Bcl-2 inhibitors, and propose a treatment strategy, prioritizing clinical trials where available.