Post-marketing surveillance of tirabrutinib for Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma in Japan.

Tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, was approved in Japan in August 2020 for the treatment of Waldenström's macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL). We report the findings of post-marketing surveillance (PMS) of tirabrutinib that was started following its approval. We conducted an all-case PMS of patients who started tirabrutinib treatment between August 21, 2020, and January 17, 2021, for WM/LPL in Japan. Safety and effectiveness data were recorded for up to 52 weeks after the first dose of tirabrutinib. Among 152 patients who started tirabrutinib, 67.1% were male, 77.6% were ≥ 65 years old, and 61.8% started treatment with tirabrutinib at 480 mg/day (once-daily). Among these 152 patients, any-grade and grade ≥ 3 adverse drug reactions (ADRs) occurred in 58.6% and 29.6% of patients, respectively. The main ADRs were platelet count decreased (9.2%) and rash (9.2%). Grade 5 ADRs were reported in four patients (2.6%). The outcomes of most ADRs associated with the safety specifications (myelosuppression, infections, interstitial lung diseases, clinically significant skin disorders, hemorrhages, hepatic function disorders, and hypersensitivities) were resolved or improved. The effectiveness was assessed by the physicians using the VIth International Workshop for Waldenström's Macroglobulinemia criteria. Among 85 patients (initial dose: 480 mg/day) included in the effectiveness analysis set, the major response and overall response rates were 63.5% and 74.1%, respectively. This PMS suggested that the safety profile of tirabrutinib for patients with WM/LPL in real-world clinical settings is in line with that observed in prior studies.