Chidamide, a Histone Deacetylase Inhibitor, Combined With R-GemOx in Relapsed/Refractory Diffuse Large B-Cell...

Area of Science:

• Oncology
• Hematology
• Pharmacology

Background:

• Histone deacetylase (HDAC) inhibitors show synergistic effects with rituximab and chemotherapy in preclinical diffuse large B-cell lymphoma (DLBCL) models.
• Relapsed/refractory (R/R) DLBCL presents a significant clinical challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate the efficacy and safety of chidamide, an oral HDAC inhibitor, in combination with the R-GemOx regimen for patients with R/R DLBCL.
• To assess the overall response rate (ORR) as the primary endpoint in this phase 2 clinical trial.

Main Methods:

• A phase 2 trial enrolled patients with transplantation-ineligible R/R DLBCL.
• Treatment involved chidamide plus R-GemOx for 6 cycles, followed by chidamide maintenance until disease progression or toxicity.
• Primary endpoint was ORR; secondary endpoints included progression-free survival (PFS) and overall survival (OS).

Main Results:

• The overall response rate (ORR) was 59.3% (95% CI: 45.0-72.4).
• Median progression-free survival (PFS) was 7.4 months and median overall survival (OS) was 23.9 months.
• Common grade 3/4 adverse events included neutropenia (40.7%), thrombocytopenia (33.3%), and leukopenia (27.8%).

Conclusions:

• Chidamide plus R-GemOx demonstrated promising anti-tumor activity and acceptable toxicity in R/R DLBCL patients.
• CREBBP and BTG2 mutations were associated with inferior response and survival outcomes in this patient cohort.