Efficacy and safety of pirtobrutinib in the Richter transformation subgroup of the multinational phase 1-2 BRUIN study

Richter transformation (RT) usually presents as an aggressive diffuse large B-cell lymphoma and is associated with a poor prognosis. The multinational phase 1-2 BRUIN study showed promising efficacy and tolerability of the reversible Bruton tyrosine kinase (BTK) inhibitor pirtobrutinib in patients with relapsed or refractory B-cell malignancies, including those who progressed on covalent BTK inhibitors. Efficacy and safety of pirtobrutinib in the BRUIN subgroup with RT have now been published. Most patients (90%) previously received RT-directed therapy. The overall response rate to pirtobrutinib monotherapy was 50.0% (95% CI 38.7-61.3) with complete response in 13% and partial response in 37%. The most common grade 3 or 4 treatment-related adverse event was neutropenia (23% of patients); there were no grade 5 TRAEs. The authors conclude that pirtobrutinib had promising safety and efficacy among patients with Richter transformation.