BTK Inhibitor and T-Cell Redirecting Immunotherapy Combination Shows Promise for Patients With R/R MCL

Results from the Phase 2 TARMAC Study

The safety and efficacy of the combination of a Bruton tyrosine kinase (BTK) inhibitor in addition to T-cell redirecting immunotherapy demonstrates promising results among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), according to data from the phase 2 TARMAC study. 

Investigators evaluated the combination of time-limited ibrutinib and CTL019 CAR-T among 20 eligible patients. Treatment of ibrutinib began before leukapheresis and continued through CAR-T manufacture for a minimum of 6 months after CAR-T administration. The median prior lines of therapy was 2. It was noted that 50% of patients were previously exposed to a BTK inhibitor. The primary end point was a 4-month post-infusion complete response (CR) rate, and secondary end points included safety and subgroup analysis based on TP53 aberrancy. 

Trial results demonstrated that the primary end point was met; 80% of patients demonstrated CR, with 70% and 40% demonstrating measurable residual disease (MRD) negativity by flow cytometry and molecular methods, respectively. It was noted that at the 13-month median follow-up, the estimated 12-month progression-free survival (PFS) was 75% and overall survival (OS) 100%. 

Adverse events were as recorded: 15 patients (75%) developed cytokine release syndrome (CRS); 12 patients (55%) with grade 1 to 2 and 3 patients (20%) with grade 3. Reversible grade 1 to 2 neurotoxicity was observed in 2 patients (10%). Efficacy was preserved irregardless of previous BTK inhibitor exposure or TP53 mutation. Deep responses corresponded with robust CAR-T expansion and a less exhausted baseline T-cell phenotype. Study authors noted that this promising research warrants further exploration. 

Adrian Minson, MBBS, Clinical Hematology, Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues concluded that, “the safety and efficacy of the combination of BTK [inhibitor] and T-cell redirecting immunotherapy appears promising and merits further exploration.”

Source:

Minson A, Hamad N, Cheah C, et al. CAR T cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: The phase 2 TARMAC study. Blood (2024) 143 (8): 673–684. doi: 10.1182/blood.2023021306