CAR T-cells and Time-Limited Ibrutinib as Treatment for Relapsed/Refractory Mantle Cell Lymphoma: Phase II TARMAC Study
- Author(s)
- Minson, AG; Hamad, N; Cheah, CY; Tam, CS; Blombery, P; Westerman, DA; Ritchie, DS; Morgan, H; Holzwart, N; Lade, S; Anderson, MA; Khot, A; Seymour, JF; Robertson, MRn; Caldwell, I; Ryland, G; Saghebi, J; Sabahi, Z; Xie, J; Koldej, RM; Dickinson, M;
- Journal Title
- Blood
- Publication Type
- epub ahead of print
- Abstract
- 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.
- Publisher
- Elsevier
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 37883795
- Publisher's Version
- https://doi.org/10.1182/blood.2023021306
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-12-21 07:38:41
Last Modified: 2023-12-21 07:46:16