According to the two-year follow-up data of Phase II, Tilabutinib, the second-generation oral Bruton's tyrosine kinase (BTK) inhibitor, is in naive (TN) and relapsed/refractory (R/R) Fahrenheit macroglobulin A study published at the annual meeting of the American Society of Hematology in 2021 that showed sustained efficacy in WM.

Tirabrutinib aims to improve the safety and effectiveness of ibrutinib, and has a more favorable toxicity profile. It was approved for TN or R/R WM in Japan in 2020. The results of an open-label, prospective, one-arm Phase II study conducted in 19 institutions in Japan, and the data deadline of the previous report is August 28, 2019, providing the basis for this approval.

This report details the results of a phase II study that enrolled 18 TN WM patients and 9 R/R WM patients. Major Response Rate (MRR) as assessed by the Independent Review Committee (IRC). Secondary endpoints are overall response rate (ORR), primary response time (TTMR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Participants with serum IgM ≥500 mg/dL received 480 mg tilabutinib once a day under fasting conditions until disease progression or unacceptable toxicity.

The median follow-up time of the TN cohort was 23.8 months, and that of the R/R group was 25.4 months. A total of 5 patients discontinued treatment due to adverse events (AE), including atypical mycobacterial infection (n = 1), disease progression (n = 1), doctor's judgment (n = 1), and subject withdrawal (n = 2). The MRR assessed by IRC was 94.4% in the TN group and 88.9% in the R/R group.

The ORR assessed by IRC was 94.4% in the TN group and 100% in the R/R group. In both cohorts, the ratio of very good partial responses or higher was 33.3%. In the TN group, the median TTMR was 1.9 months (range = 1-20.3), while the R/R group was 2.1 months (range = 1-3.7). In both treatment groups, the median PFS, OS and DOR were not reached. The two-year PFS rates for the TN and R/R cohorts were 94.4% and 88.9%, respectively. In patients who continued to receive treatment, a continuous decrease in IgM was observed.

In the two treatment groups, the most common AEs were skin rash (44.4%), neutropenia (33.3%) and nasopharyngitis (25.9%). The most common grade ≥3 AEs are neutropenia (22.2%), lymphopenia (18.5%), and leukopenia (11.1%). A new treatment-related hypertriglyceridemia AE was observed during the follow-up period.