A new conditioning regimen with chidamide, cladribine, gemcitabine and busulfan significantly improve the outcome of high-risk or relapsed/refractory non-Hodgkin's lymphomas.

Abstract

Previous studies highlight the need for a more active conditioning therapy in high-risk or refractory and relapsed lymphomas. Our preclinical research shows that histone deacetylase inhibitors, such as either vorinostat or chidamide, sensitize lymphoma cells to the cytotoxic combination of cladribine, gemcitabine and busulfan, leading to cell apoptosis. To evaluate the efficacy of this chidamide-cladribine-gemcitabine-busulfan (ChiCGB) combination as a new conditioning therapy, we conducted a Phase II trial, as described here. Patients with high-risk, relapsed/refractory lymphomas received ChiCGB as conditioning therapy, after transplantation with autologous peripheral stem cells. The sample comprised 105 patients in total: 60 with B-cell non-Hodgkin lymphomas (B-NHL) and 45 with T-cell or natural killer/T-cell lymphoma (NK/T). All patients eventually achieved full hematopoietic recovery. Neutrophils and platelets were engrafted at a median of 10 days (8-14) and 13 days (8-38), respectively. There was no transplant-related mortality within 100 days of transplant. Neutropenic fever, mucositis and atopic dermatitis were the observed nonhematologic toxicities. At a median follow-up of 35.4 months, 80.6% of the patients presented with no tumor progression, and the overall survival (OS) reached as high as 86.1%. Concerning the OS rate, 94.5% of patients with B-NHL and 75.4% of patients with T-cell or NK/T lymphomas survived. These findings demonstrate the safety and validity of the proposed combined therapy for high-risk and refractory/relapsed lymphomas. Our study was registered on the Clinical Trial Registry (clinicaltrials.gov, NCT03151876).

• Authors: Jie Ji, Zhigang Liu, Pu Kuang, Tian Dong, Xinchuan Chen, Jian Li, Chuanli Zhang, Jiazhuo Liu, Li Zhang, Kai Shen, Ting Liu
• Journal: International journal of cancer (Int J Cancer) Vol. 149 Issue 12 Pg. 2075-2082 (12 15 2021) ISSN: 1097-0215 [Electronic] United States
• PMID: 34398971 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 UICC.

Chemical References

• Aminopyridines
• Benzamides
• Deoxycytidine
• Cladribine
• N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
• Busulfan
• Gemcitabine

Topics

• Adolescent
• Adult
• Aged
• Aminopyridines (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Benzamides (administration & dosage, adverse effects)
• Busulfan (administration & dosage, adverse effects)
• Cladribine (administration & dosage, adverse effects)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Drug Resistance, Neoplasm
• Female
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation
• Humans
• Lymphoma, Non-Hodgkin (mortality, therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (mortality, therapy)
• Progression-Free Survival
• Transplantation Conditioning (adverse effects, methods)
• Transplantation, Autologous
• Young Adult
• Gemcitabine