CD19-directed chimeric antigen receptor T-cells achieve high response rates in patients with relapsed or refractory mantle cell lymphoma. However, their use is associated with significant toxicity, relapse is a concern, and their broad tractability is unclear. Pre-clinical and clinical data support a beneficial synergistic effect of ibrutinib on apheresis product fitness, CAR-T expansion and toxicity. We evaluated the combination of time-limited ibrutinib and CTL019 CAR-T in 20 patients with MCL on the phase II TARMAC study. Ibrutinib commenced prior to leukapheresis and continued through CAR-T manufacture and for a minimum of 6 months after CAR-T administration. The median prior lines of therapy was 2, 50% of patients were previously exposed to a BTKi. The primary endpoint was complete response rate 4-months post-infusion, and secondary endpoints included safety, and subgroup analysis based on TP53 aberrancy. The primary endpoint was met; 80% of patients demonstrated CR, with 70% and 40% demonstrating measurable residual disease negativity by flow cytometry and molecular methods, respectively. At a median follow up of 13 months, the estimated 12-months PFS was 75% and OS 100%. Fifteen patients (75%) developed cytokine release syndrome, grade 1-2 in 12 (55%) and grade 3 in 3 (20%). Reversible grade 1-2 neurotoxicity was observed in 2 patients (10%). Efficacy was preserved irrespective of prior BTKi exposure or TP53 mutation. Deep responses correlated with robust CAR-T expansion and a less exhausted baseline T-cell phenotype. Overall, the safety and efficacy of the combination of BTKi and T-cell redirecting immunotherapy appears promising and merits further exploration. ClinicalTrials.gov NCT04234061