Long-term follow-up of patients with mantle cell lymphoma (MCL) treated with the selective Bruton’s tyrosine kinase inhibitor tirabrutinib (GS/ONO-4059)

Abstract

To the Editor: Recent therapeutic advances for mantle cell lymphoma (MCL) include inhibitors of Bruton’s tyrosine kinase (BTK), a critical component in the B-cell receptor signaling pathway [1, 2]. Remarkably, approximately two thirds of patients with relapsed/refractory (R/R) MCL treated with ibrutinib, the first-in-class BTK inhibitor, achieve a durable response [3–5]. However, ibrutinib treatment also commonly produces off-target adverse events (AEs) such as bleeding, atrial fibrillation, diarrhea, and infection. Second-generation BTK inhibitors with greater selectivity include tirabrutinib (GS/ONO-4059), acalabrutinib, and BGB-3111 [6]. In 2017, acalabrutinib received FDA approval for the treatment of MCL based on a complete response (CR) rate of 40% and an overall response rate (ORR) of 81% at a median follow-up of 15.2 months in a phase 2 study [7]. Tirabrutinib has demonstrated significant activity without major drug-related toxicities in a phase 1 study in R/R B-cell malignancies [8] and on extended, 3-year follow-up of patients with chronic lymphocytic leukemia [9]. Here, we provide 3-year follow-up data from patients with MCL in the phase 1 tirabrutinib extension study (NCT02457559).