Does BTKi improve CAR T-cell in MCL?

In this issue of Blood, Minson et al present the first clinical study investigating the combinatorial use of a Bruton tyrosine kinase inhibitor (BTKi) with CD19 chimeric antigen receptor (CAR) T cells in patients with relapsed/ refractory mantle cell lymphoma (MCL), a cohort with historically poor outcomes.1 Despite encouraging results in the phase 2 ZUMA-2 and TRANSCEND NHL-001 studies, which studied the use of brexucabtagene autoleucel and lisocabtagene maraleucel (liso-cel), respectively, there is a significant unmet clinical need to improve MCL outcomes after immune effector cell therapy.2,3 A rationally designed combinatorial strategy using approved drugs with proven efficacy on MCL has the potential to deepen responses without relying on more intensive preclinical validation required for new drug approval. Many agents, ranging from small molecular inhibitors to monoclonal antibodies, have been investigated to boost CAR T-cell activity, yet none has reached phase 3. Requisite early-phase studies must demonstrate that the added agent does not interfere with antitumor effect or potentiate toxicities.