地尼白介素妥西-Cxdl（一种纯度更高的地尼白介素妥西制剂）在复发或难治性皮肤T细胞淋巴瘤患者中的疗效和安全性

Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma.

作者信息

Foss Francine M, Kim Youn H, Prince H Miles, Akilov Oleg E, Querfeld Christiane, Seminario-Vidal Lucia, Fisher David C, Kuzel Timothy M, Yannakou Costas K, Geskin Larisa J, Feldman Tatyana, Sokol Lubomir, Allen Pamela Blair, Dang Nam Hoang, Cabanillas Fernando, Wong Henry K, Ooi Chean Eng, Xing Dongyuan, Sauter Nicholas, Singh Preeti, Czuczman Myron, Duvic Madeleine

机构信息

Yale University School of Medicine, New Haven, CT.

Departments of Dermatology & Medicine, Stanford Cancer Center, Stanford, CA.

出版信息

J Clin Oncol. 2025 Apr;43(10):1198-1209. doi: 10.1200/JCO-24-01549. Epub 2024 Dec 19.

DOI:10.1200/JCO-24-01549

PMID:39700456

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11949209/

Abstract

PURPOSE

Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

PATIENTS AND METHODS

In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. The primary efficacy end point was objective response rate (ORR) using the Global Response Score. Secondary end points were duration of response (DOR), time to response (TTR), skin tumor burden, and safety and tolerability.

RESULTS

The PEAS included 69 patients (median age, 64.0 years). The ORR was 36.2% (95% CI, 25.0 to 48.7), including 8.7% with complete response. The median DOR was 8.9 months (95% CI, 5.0 to not estimable), and the median (Q1-Q3) TTR was 1.4 (0.7-2.1) months. A total of 84.4% of patients showed decreased skin tumor burden, with 48.4% showing a ≥50% decrease. Treatment-emergent adverse events (TEAEs) of special interest, most of which were grade 1 or 2, included infusion reaction (73.9%), hypersensitivity (68.1%), hepatotoxicity (36.2%), and capillary leak syndrome (20.3% [grade ≥3, 5.8%]). Other common TEAEs were nausea (43.5%) and fatigue (31.9%).

CONCLUSION

Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with R/R CTCL.

摘要

目的

地尼白介素-匹伏妥昔（DD）-cxdl是一种融合蛋白，由白喉毒素A和B片段以及人白细胞介素-2组成。这项III期、多中心、开放标签、单臂注册试验评估了DD-cxdl在复发/难治性（R/R）皮肤T细胞淋巴瘤（CTCL）患者中的疗效和安全性。

患者与方法

在主要研究中，在进行剂量探索导入期后，每21天静脉注射DD-cxdl，每日一次（共5天；9µg/kg/d），最多进行8个周期。主要疗效分析集（PEAS）中的患者需患有IA-IIIB期CTCL（蕈样肉芽肿和/或塞扎里综合征）且至少接受过≥一种先前的全身治疗。主要疗效终点是使用整体反应评分的客观缓解率（ORR）。次要终点是缓解持续时间（DOR）、反应时间（TTR）、皮肤肿瘤负担以及安全性和耐受性。

结果

PEAS纳入了69例患者（中位年龄64.0岁）。ORR为36.2%（95%CI，25.0至48.7），包括8.7%的完全缓解患者。中位DOR为8.9个月（95%CI，5.0至无法估计），中位（Q1-Q3）TTR为1.4（0.7-2.1）个月。共有84.4%的患者皮肤肿瘤负担减轻，其中48.4%的患者减轻≥50%。特别关注的治疗中出现的不良事件（TEAE），大多数为1级或2级，包括输液反应（73.9%）、超敏反应（68.1%）、肝毒性（36.2%）和毛细血管渗漏综合征（20.3%[≥3级，5.8%]）。其他常见的TEAE为恶心（43.5%）和疲劳（31.9%）。