Tucidinostat Plus R-CHOP Improves Outcomes in Double-Expressor DLBCL
Key Takeaways
- Tucidinostat plus R-CHOP was associated with improved event-free survival versus placebo plus R-CHOP in newly diagnosed MYC/BCL2 double-expressor DLBCL.
- The tucidinostat regimen was also associated with a higher complete response rate at 73.0% versus 61.8%.
- Toxicity increased with tucidinostat, but treatment-related adverse effects were generally manageable with supportive care.
The randomized, double-blind, placebo-controlled study was conducted across 40 centers in China. Patients had frontline diffuse large B-cell lymphoma defined by MYC and BCL2 coexpression. The findings came from a biomarker-defined first-line treatment setting.
Investigators enrolled 423 eligible patients with newly diagnosed MYC/BCL2 double-expressor diffuse large B-cell lymphoma and randomly assigned them 1:1 to study treatment. The multicenter design spanned participating sites across China. Participants received oral tucidinostat, a selective histone deacetylase inhibitor, or matching placebo, and all patients received 6 cycles of R-CHOP. Tucidinostat was given at 20 mg on days 1, 4, 8, and 11 of each 21-day cycle. Median age was 63 years, 47.5% were male, and patients in complete response continued assigned maintenance for up to 24 weeks in the registered trial NCT04231448.
Event-free survival was the primary end point; secondary end points included complete response, progression-free survival, disease-free survival, overall survival, and tolerability. The stratified hazard ratio for event-free survival was 0.72, with a 95% CI of 0.54 to 0.96 and P=.02. At 2 years, event-free survival was 60.3% with tucidinostat plus R-CHOP and 50.5% with placebo plus R-CHOP. Complete response rates were 73.0% and 61.8%, an absolute difference of 11.1% with a 95% CI of 2.3% to 20.0%.
Enrollment occurred from May 21, 2020, through July 25, 2022, with follow-up through June 26, 2025. Median follow-up from randomization was 41.3 months. Toxicity increased with the tucidinostat regimen, but treatment-related adverse effects were generally manageable with supportive care.
During follow-up, improved efficacy was accompanied by higher toxicity in this first-line MYC/BCL2 double-expressor population.