IntroductionSecond-generation Bruton's tyrosine kinase (BTK) inhibitors, acalabrutinib and zanubrutinib, are preferred agents for the treatment of relapsed and/or refractory mantle cell lymphoma (MCL) over first-generation BTK inhibitor, ibrutinib. The comparative safety and efficacy of these two agents have not been studied. Currently, the decision between using one second-generation BTK inhibitor over the other is largely dependent on provider preference, cost, organ dysfunction, presence of drug-drug interactions, adherence considerations, and theorized differences in safety outcomes due to the lack of head-to-head trials in MCL.MethodsThis retrospective, observational study seeks to provide real-world data on the safety and efficacy of second-generation BTK inhibitors in the setting of relapsed and/or refractory MCL.ResultsThirty-eight patients treated with a second-generation BTK inhibitor were evaluated. Ten percent of patients experienced a select adverse drug event (ADE) in the acalabrutinib group that included hypertension and major hemorrhage with no patients experiencing a select ADE in the zanubrutinib group.ConclusionsResults support historical data that acalabrutinib and zanubrutinib have a more favorable safety profile compared to ibrutinib in MCL.