Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma.

Abstract

BACKGROUND:

Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2).

RESULTS:

Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52-79) and 83% (95% CI 68-91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3-4 neutropenia was reported in 171, grade 3-4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported.

CONCLUSION:

CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

• Authors: Mu-Chen Zhang, Ying Fang, Li Wang, Shu Cheng, Di Fu, Yang He, Yan Zhao, Chao-Fu Wang, Xu-Feng Jiang, Qi Song, Peng-Peng Xu, Wei-Li Zhao
• Journal: Clinical epigenetics (Clin Epigenetics) Vol. 12 Issue 1 Pg. 160 (10 23 2020) ISSN: 1868-7083 [Electronic] Germany
• PMID: 33097085 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCL2 protein, human
• Benzamides
• Biomarkers
• HBI-8000
• Histone Deacetylase Inhibitors
• MYC protein, human
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-myc
• Pyridines
• R-CHOP protocol
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• CREB-Binding Protein
• CREBBP protein, human
• E1A-Associated p300 Protein
• EP300 protein, human
• Prednisone

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Benzamides (administration & dosage, adverse effects, therapeutic use)
• Biomarkers (analysis)
• CREB-Binding Protein (drug effects, metabolism)
• Case-Control Studies
• Cyclophosphamide (administration & dosage, therapeutic use)
• Doxorubicin (administration & dosage, therapeutic use)
• E1A-Associated p300 Protein (drug effects, metabolism)
• Epigenomics
• Female
• Histone Deacetylase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Humans
• Lymphoma, Large B-Cell, Diffuse (diagnosis, drug therapy, genetics, pathology)
• Male
• Middle Aged
• Mutation
• Phenotype
• Prednisone (administration & dosage, therapeutic use)
• Prognosis
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Proto-Oncogene Proteins c-myc (metabolism)
• Pyridines (administration & dosage, adverse effects, therapeutic use)
• Rituximab (administration & dosage, therapeutic use)
• Survival Rate
• Treatment Outcome
• Vincristine (administration & dosage, therapeutic use)