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 highrisk 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-cladribinegemcitabine-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).

Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

“…Chidamide with cladribine, gemcitabine and busulfan were administrated as conditioning therapy for autologous transplantation. The results showed a high OS rate of 86.1% at a median follow‐up of 35.4 months 34 Downregulation or loss of CD20 expression may cause treatment failure of rituximab in DLBCL. Chidamide was reported to significantly increase CD20 surface expression in DLBCL cell lines 35 .…”

Therapeutic potential of tucidinostat, a subtype-selective HDAC inhibitor, in cancer treatment

“…A phase II clinical trial assessed the combination of tucidinostat, cladribine, gemcitabine, and busulfan (ChiCGB) in 105 patients (60 with B-cell non-Hodgkin lymphomas (B-NHL), and 45 with T-cell, or natural killer/T-cell lymphoma (NKT) followed by autologous stem cell transplant (ASCT) (Ji et al, 2021). The 4-year OS was 86.1%, which is significantly higher than the OS of traditional therapies (less than 70%), as reported in previous studies (Stiff et al, 2013).…”

The Status and Prospects of Epigenetics in the Treatment of Lymphoma

“…The median PFS and OS were 6 months and 23 months, respectively (2021 ICML.Abstract No.209). A new conditioning regimen with chidamide, cladribine, gemcitabine and busulfan (ChiCGB), significantly improved the outcome of high-risk or relapsed/ refractory NHL (r/r NHL) (165). All 105 patients with high-risk, relapsed/refractory lymphoma who received ChiCGB as a conditioning therapy after transplantation of autologous peripheral stem cells, achieved complete hematopoietic recovery.…”