Tirabrutinib Meta-Analysis Reports 72.5% Response in B-Cell Malignancies

Pooled data showed an overall response rate (ORR) of 72.5% with tirabrutinib monotherapy in B-cell lymphomas and leukemia, according to a meta-analysis of seven prospective clinical trials published in Frontiers in Pharmacology.

Tirabrutinib is a second-generation, irreversible, highly selective Bruton's tyrosine kinase (BTK) inhibitor. The investigators noted that the safety and efficacy of tirabrutinib monotherapy had not been systematically assessed. They searched Embase, PubMed, Web of Science, and the Cochrane Library through February 20, 2024, for prospective trials evaluating the drug as monotherapy.

The included trials enrolled 301 patients primarily with chronic lymphocytic leukemia (CLL), primary central nervous system lymphoma (PCNSL), mantle cell lymphoma (MCL), and Waldenström's macroglobulinemia (WM), most with relapsed or refractory disease. Six were phase 1 or 2 single-arm studies, and one was a phase 4 multicenter study. Pooled complete response, partial response, and stable disease rates were 18.6%, 41.1%, and 13.8%, respectively. The highest ORR, 96.3%, was reported in a WM study, and the longest median progression-free survival, 38.5 months, in a CLL study.

Neutropenia was the most common adverse event (AE) of any grade (26.7%) and of grade 3 or higher (18.4%). Diarrhea (26.0%) and rash (24.9%) were the next most frequent all-grade AEs. The authors reported that patients with PCNSL and WM were most susceptible to skin-related AEs. Only two studies reported atrial fibrillation, at rates of 7% and 3%.

The authors concluded that tirabrutinib monotherapy demonstrates a manageable safety profile and promising efficacy, but they said larger, higher-quality randomized controlled trials are needed to confirm the findings. They noted that the included studies were not designed as randomized controlled trials, that the effect of drug dosage was not evaluated, and that the pooled partial response result was not robust in sensitivity analysis.

Source: Wang J, Cheng H, Sun Y, et al. Efficacy and safety of tirabrutinib monotherapy in relapsed or refractory B-cell lymphomas/leukemia: a meta-analysis. Front Pharmacol. 2025;16:1559056. doi:10.3389/fphar.2025.1559056