Multicenter phase 3 trial of addition of tucidinostat to first-line R-CHOP in MYC/BCL2 double-expressor diffuse large B-cell lymphoma

MYC/BCL2 double-expressor lymphoma (DEL) is a distinct population of diffuse large B-cell lymphoma defined by MYC and BCL2 coexpression. DEL is associated with poor prognosis after standard R-CHOP immunochemotherapy. The phase 3 DEB trial, at 40 centers in China, evaluated addition of the oral histone deacetylase inhibitor tucidinostat to first-line R-CHOP in patients with DEL. The trial enrolled 423 eligible patients, who were randomized 1:1 to receive oral tucidinostat 20 mg on days 1, 4, 8, and 11 of 21-day cycles or matching placebo, plus 6 cycles of R-CHOP. Patients with complete response received either tucidinostat or placebo maintenance for up to 24 weeks. The primary endpoint was event-free survival (EFS). The median duration of follow-up was 41.3 months. The tucidinostat group had a 28% lower risk of disease progression, relapse after complete response, death, or initiation of new therapy for residual disease compared with the placebo group (sHR 0.72; p=0.2), with a 2-year EFS rate of 60.3% versus 50.5%, respectively. The complete response rate was 73.0% versus 61.8% (difference 11.1%; 9% CI 2.3-20.0), respectively. The increased toxicity in the tucidinostat group was generally manageable with supportive care. The authors conclude that addition of tucidinostat to first-line R-CHOP significantly improved EFS, with manageable toxicity in patients with newly diagnosed DEL.