A report on 2 years of follow-up data from a phase 2 study found tirabrutinib continued to show efficacy in patients with treatment-naïve (TN) or relapse/refractory (R/R) Waldenström’s macroglobulinemia (WM); these findings were presented at the 2021 Annual American Society of Hematology (ASH) Meeting.

Tirabrutinib is a second-generation oral Bruton’s tyrosine kinase (BTK) inhibitor that is more selective for BTK than first-generation BTK inhibitors, such as ibrutinib, said Kenshi Suzuki, MD, PhD, Department of Hematology, Japanese Red Cross Medical Center, Toyko, Japan, and co-investigators.

“Tirabrutinib has been designed to improve the safety and efficacy of ibrutinib, and has been suggested to have a more favorable toxicity profile, including in atrial fibrillation (Af) and bleeding events,” continued Dr Suzuki.

In 2020, tirabrutinib was approved in Japan for use in TN or R/R WM based off of results from an open-label, prospective, single-arm phase 2 study throughout 19 facilities in Japan. The study focused on 18 patients with TN WM (cohort A) and 9 patients with R/R WM (cohort B), all having serum IgM ≥ 500 mg/dL. Patients received 480 mg of tirabrutinib under fasting conditions once a day until disease progression or unacceptable toxicity.

The primary end point was major response rate (MRR) assessed by an independent review committee (IRC), according to the VIth International Workshop on WM (IWWM) criteria. Secondary endpoints included overall response rate (ORR), time to major response (TTMR), duration of response (DOR), progression free survival (PFS), overall survival (OS), and safety.

The MRR was 88.9 percent in both cohort A and B. In a median follow-up period of 6.5 months (cohort A) and 8.3 months (cohort B), the ORR was 94.4 percent and 100 percent, respectively. Data cutoff for this study was August 28, 2019.

Thus, Dr Suzuki reported on 2-year follow-up data of this study. The data cutoff was February 1, 2021, after a median follow-up period of 23.8 months in cohort A and 25.4 months in cohort B.

During the extended follow-up period, out of 27 total patients, 5 discontinued tirabrutinib treatment due to adverse events. IRC-assessed MRR was 94.4 percent (95% CI, 72.7-99.9) in cohort A and 88.9 percent (95% CI, 51.8-99.7) in cohort B. The IRC-assessed ORR was 94.4 percent (95% CI, 72.7-99.9), and 100 percent (95% CI, 66.4-100.0), respectively. For cohort A, the median TTMR was 1.9 months (range 1-20.3), and for cohort B was 2.1 months (range 1-3.7). The median PFS, OS, and DOR were not met by either cohort. The 2-year PFS rate was 94.4 percent in cohort A, and 88.9 percent in cohort B. The 2-year OS rate was 100% for both cohorts.

Dr Susuki and co-investigators said there were continued reductions of IgM observed in patients who stayed on tirabrutinib treatment. However, 3 patients that discontinued treatment (other reasons than withdrawal by subject) had an increase in IgM after they stopped treatment.

Out of the entire study population, the most common adverse events (AEs) of grade < 3 were rash (44.4%), neutropenia (33.3%), and nasopharyngitis (25.9%). The most common AEs of grade ≥ 3 were neutropenia (22.2%), lymphopenia (18.5%), and leukopenia (11.1%). Two patients experienced Af, and 9 experienced bleeding AE. During the follow-up, there were no new grade ≥ 3 treatment-related AEs observed, except for hypertriglyceridemia in 1 patient.

“Tirabrutinib demonstrated sustained efficacy in TN and R/R WM patients during the 2-year follow-up period. Additionally, no. new safety signals for tirabrutinib were identified compared to previous reports. Tirabrutinib is a useful treatment option for WM,” concluded Dr Suzuki et al.—Emily Bader

Suzuki K, Sekiguchi N, Rai S, et al. Two-year follow-up data of phase II study of tirabrutinib, a second-generation Bruton’s tyrosine kinase inhibitor, in patients with treatment-naïve or relapsed/refractory Waldenström’s macroglobulinemia. Presented at: the 2021 ASH Annual Meeting. Dec 11-14, 2021. Abstract 1352.