Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2024 Jul 8;15:1415597. doi: 10.3389/fimmu.2024.1415597. eCollection 2024.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by hyperinflammation and organ failure, with a high mortality rate. Current first-line treatments for adult patients have limited efficacy and significant toxicity. The novel selective histone deacetylase inhibitor (HDACi), chidamide, has shown promise in preclinical studies for the potential treatment of HLH.
An open-label, single-center study was conducted to evaluate the efficacy and safety of chidamide in combination with etoposide and glucocorticoids for the treatment of HLH in adult patients. Seventeen patients who fulfilled at least five of the eight HLH-2004 criteria were enrolled and treated with the combination therapy. The primary outcome was overall response rate (ORR), and secondary outcomes included survival, safety and tolerability, and changes in laboratory indicators.
A total of 17 HLH patients who met the inclusion criteria were enrolled in this study, with a male to female ratio of 1.8:1. The age range at enrollment was 31 to 71 years old, with a median age of 52 years old. The ORR was 76.5% (13/17 patients), with a complete response (CR) rate of 17.6% (3/17 patients) and a partial response (PR) rate of 58.8% (10/17 patients). The median overall survival (OS) was not achieved, with OS at 6 months and 12 months being 81% and 65%, respectively. The median progression free survival (PFS) was not achieved, with PFS at 6 months and 12 months being 68% and 55%, respectively. Hematologic toxicities is the most common. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. The results showed that the levels of sCD25, platelets, aspartate aminotransferase, lactate dehydrogenase, and albumin in these patients were significantly improved 3 weeks after treatment.
The addition of chidamide to etoposide and glucocorticoids may be a promising new treatment option for patients with HLH, with a high ORR, manageable safety profile, and significant improvement in laboratory indicators. Further research is needed to confirm these findings and determine the optimal dosing and duration of therapy.
噬血细胞性淋巴组织细胞增生症（HLH）是一种以炎症反应和器官衰竭为特征的危及生命的疾病，死亡率很高。目前，成人患者的一线治疗方法疗效有限，毒性较大。新型选择性组蛋白去乙酰化酶抑制剂（HDACi）西达本胺在 HLH 的临床前研究中显示出了潜在的治疗效果。
进行了一项开放标签、单中心研究，以评估西达本胺联合依托泊苷和糖皮质激素治疗成人 HLH 的疗效和安全性。共纳入了 17 名满足 HLH-2004 标准中至少 5 项标准的患者，并接受联合治疗。主要终点为总缓解率（ORR），次要终点包括生存率、安全性和耐受性以及实验室指标的变化。
本研究共纳入了 17 名符合纳入标准的 HLH 患者，男女比例为 1.8:1。入组时年龄范围为 31-71 岁，中位年龄为 52 岁。ORR 为 76.5%（13/17 例），完全缓解（CR）率为 17.6%（3/17 例），部分缓解（PR）率为 58.8%（10/17 例）。中位总生存期（OS）未达到，6 个月和 12 个月的 OS 率分别为 81%和 65%。中位无进展生存期（PFS）未达到，6 个月和 12 个月的 PFS 率分别为 68%和 55%。血液学毒性是最常见的不良反应。安全性良好，仅观察到少数 3/4 级毒性反应。结果显示，这些患者在治疗后 3 周时 sCD25、血小板、天门冬氨酸氨基转移酶、乳酸脱氢酶和白蛋白水平显著改善。
西达本胺联合依托泊苷和糖皮质激素治疗 HLH 可能是一种有前途的新治疗选择，具有较高的 ORR、可管理的安全性和显著改善的实验室指标。需要进一步的研究来证实这些发现并确定最佳的治疗剂量和疗程。
