Original Investigation

Tucidinostat Plus R-CHOP vs R-CHOP in MYC/BCL2 Double-Expressor Diffuse Large B-Cell Lymphoma

JAMA 10.1001/jama.2026.4199

April 22, 2026 at 11:00 AM EDT

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Does adding the histone deacetylase inhibitor tucidinostat to R-CHOP improve clinical outcomes in patients with newly diagnosed MYC/BCL2 double-expressor lymphoma?In this randomized phase 3 clinical trial that included 423 patients, event-free survival was significantly improved with tucidinostat plus R-CHOP compared with placebo plus R-CHOP (hazard ratio, 0.72), with a generally manageable safety profile.These findings support the use of an epigenetic modulator (tucidinostat) combined with R-CHOP as a first-line treatment for MYC/BCL2 double-expressor lymphoma, a biologically distinct entity of diffuse large B-cell lymphoma associated with poor prognosis after standard R-CHOP immunochemotherapy.

Corresponding Authors: Wei-Li Zhao, MD, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Rd, Shanghai 200025, China (zhao.weili@yahoo.com); Jun Zhu, MD, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Fucheng Rd No. 52, Beijing 100142, China (zhujun@csco.org.cn).

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