- Tirabrutinib (ONO/GS-4059), a second-generation Bruton’s tyrosine kinase inhibitor shows a high response rate in patients with treatment-naïve (TN) or relapsed/refractory (R/R) Waldenström's macroglobulinemia, with a manageable safety profile.
Why this matters
- Waldenström's macroglobulinemia is an incurable lymphoplasmacytic lymphoma with poor outcomes, but some favorable responses have been observed with the first FDA approved Bruton’s tyrosine kinase inhibitor ibrutinib.
- A prospective, multicenter phase 2 study of 27 patients (median age, 71 years) with TN (n=18) or R/R (n=9) Waldenström's macroglobulinemia.
- Patients received tirabrutinib 480 mg once daily until disease progression, unacceptable toxicity, or death.
- Primary endpoint: major response rate (MRR, ≥ partial response [PR]).
- Secondary endpoint: overall response rate (ORR; ≥ minor response [MR]), time to major response (TTMR), duration of response (DOR), PFS, OS, and safety.
- Funding: Ono Pharmaceutical Co., Ltd.
- The median follow-up duration was 6 months.
- MRR was 77.8% (95% CI, 52.4%-93.6%) in TN and 88.9% (95% CI, 51.8%-99.7%) in R/R groups.
- ORR was 94.4% (95% CI, 72.7%-99.9%) in TN and 100% (95% CI, 66.4%-100.0%) in R/R groups.
- Median DOR, PFS, and OS were not reached.
- The most common any grade adverse events (AEs) were rash (41%), neutropenia (22%), and leukopenia (15%).
- The most frequent grade ≥3 AEs were neutropenia (7.4%), leukopenia, lymphopenia, atypical mycobacterial infection, rash erythematous, and erythema multiforme (3.7% each).
- No grade 4-5 AE was reported.
- Small study group.