BTK Inhibitors and CAR T-Cell Therapy in Treating Mantle Cell Lymphoma-Finding a Dancing Partner

Abstract

Purpose of review: This review focuses on the feasibility of combining Bruton's tyrosine kinase (BTK) inhibitors (BTKis) with chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL). Potential scenarios for combination treatment with these agents are presented.

Recent findings: BTKis and CAR T-cell therapy have revolutionized the treatment paradigm for R/R MCL. Ibrutinib, acalabrutinib, and zanubrutinib are covalent irreversible BTKis approved for R/R MCL. Brexucabtagene autoleucel was the first CAR T-cell therapy approved for R/R MCL based on findings from the ZUMA-2 trial. There is evidence to suggest that combination treatment with BTKis and CAR T-cell therapy may improve CAR T-cell efficacy. As BTKis and CAR T-cell therapy become mainstays in R/R MCL therapy, combination treatment strategies should be evaluated for their potential benefit in R/R MCL.

Keywords: Bruton’s tyrosine kinase; Chimeric antigen receptor T-cell therapy; Combination therapy; Relapsed/refractory mantle cell lymphoma.