Chidamide plus R-GDP for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for autologous transplantation: A prospective, single-arm, phase II study

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2024-08-29 DOI:10.1002/cam4.70142

Guang-Liang Chen, Kai Xue, Qunling Zhang, Zu-guang Xia, Jia Jin, Ran Li, Yizhen Liu, Fangfang Lv, Xiaonan Hong, Xiaoqiu Li, Junning Cao

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引用次数: 0

Abstract

Background

In relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), a negative prognosis is frequently linked to heightened epigenetic heterogeneity. Chidamide, a selective histone deacetylase inhibitor, shows promise as a targeted therapy for R/R DLBCL by targeting abnormal epigenetic changes associated with poor prognosis.

Methods

A cohort of 27 ineligible patients with R/R DLBCL participated in an open — label, single — arm study. Chidamide was administered orally at a dose of 30 mg twice weekly for one week during the induction monotherapy phase. The subsequent combination therapy phase involved oral chidamide at a dose of 20 mg twice weekly for two weeks, followed by a one-week discontinuation period, in conjunction with intravenous R-GDP every 21 days.

Results

Among the cohort of 31 patients who underwent screening (median age: 67 years), 27 were ultimately included in the study, with 14 individuals successfully completing six cycles of C-R-GDP treatment. The overall best objective response rate was determined to be 79.1% (95% CI: 75.1%–83.3%), comprising a complete response rate of 45.8% (95% CI: 41.6%–49.9%) and a partial response rate of 33.3% (95% CI: 29.3%–37.4%). Within the subgroup of 14 patients who completed the full treatment regimen, the best objective response rate reached 100%, with 71.4% achieving complete response (n = 10) and 28.6% achieving partial response (n = 4). The median follow-up period for these patients was 17.0 months, ranging from 3.5 to 55 months. Progression-free survival was 5.9 months and overall survival was 48.3 months. Anemia was the most common adverse event, affecting all patients. Thrombocytopenia led to treatment interruption or dose reduction in 13 patients. Other common adverse events included hypocalcemia, hyponatremia, and hypokalemia. Three patients experienced grade 3 pneumonitis and one had grade 3 skin rash.

Conclusions

Chidamide combined with R-GDP is a safe and effective treatment option for patients with R/R DLBCL who are not eligible for autologous stem cell transplantation.

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治疗不符合自体移植条件的复发/难治性弥漫大B细胞淋巴瘤患者的千达酰胺加R-GDP：前瞻性单臂II期研究

背景在复发/难治性（R/R）弥漫大 B 细胞淋巴瘤（DLBCL）中，不良预后往往与表观遗传异质性增高有关。千达酰胺是一种选择性组蛋白去乙酰化酶抑制剂，通过靶向治疗与不良预后相关的异常表观遗传变化，有望成为治疗R/R DLBCL的靶向疗法。方法 27名不符合条件的R/R DLBCL患者参加了一项开放标签、单臂研究。在诱导单药治疗阶段，患者口服氯达酰胺，剂量为30毫克，每周两次，持续一周。随后的联合治疗阶段包括口服氯达胺，剂量为20毫克，每周两次，持续两周，然后停药一周，同时静脉注射R-GDP，每21天一次。结果在接受筛查的31名患者（中位年龄：67岁）中，27人最终被纳入研究，其中14人成功完成了6个周期的C-R-GDP治疗。总体最佳客观反应率为 79.1%（95% CI：75.1%-83.3%），其中完全反应率为 45.8%（95% CI：41.6%-49.9%），部分反应率为 33.3%（95% CI：29.3%-37.4%）。在完成全部治疗方案的 14 例患者分组中，最佳客观反应率达到 100%，其中 71.4% 实现完全反应（10 例），28.6% 实现部分反应（4 例）。这些患者的中位随访期为 17.0 个月，从 3.5 个月到 55 个月不等。无进展生存期为5.9个月，总生存期为48.3个月。贫血是最常见的不良反应，影响到所有患者。血小板减少导致13名患者中断治疗或减少剂量。其他常见的不良反应包括低钙血症、低钠血症和低钾血症。3 名患者出现 3 级肺炎，1 名患者出现 3 级皮疹。结论对于不符合自体干细胞移植条件的R/R DLBCL患者，奇达胺联合R-GDP是一种安全有效的治疗选择。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.

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