An evaluation of denileukin diftitox for the treatment of relapsed or refractory cutaneous T-cell lymphoma.

IF 3.6 3区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Expert Opinion on Biological Therapy Pub Date : 2025-06-09 DOI:10.1080/14712598.2025.2517853

Amrita Goyal, Francine M Foss

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引用次数: 0

Abstract

Introduction: Denileukin difitox (DD), a recombinant cytotoxic fusion protein composed of full-length human interleukin-2 (IL-2) conjugated to diphtheria toxin's A and B subunits, has shown activity in patients with relapsed and refractory (R/R) mycosis fungoides and the Sezary Syndrome (MF/SS) whose tumor cells expressed CD25, with response rates of 30-44% in advanced and earlier (Stage I-III) stage patients respectively.

Areas covered: Recently a newer version of DD with improved purity and bioactivity (DD-cxdl) was developed. A registrational trial of D-cxdl showed similar response rates in R/R MF/SS. The purpose of this review is to describe efficacy and safety data surrounding these medications and highlight the equivalency of these two drugs.

Expert opinion: Both DD and DD-cxdl demonstrate activity in R/R MF/SS with higher response rate in tumor and plaque stage disease. Adverse events grade ≥ 3 included infusion reactions in 8%, elevated hepatic transaminases in 22%, and capillary leak syndrome in 8%. In addition to direct targeting of CD25 expressing tumor cells, both drugs are also capable of depleting immunoregulatory T-cells. A clinical trial of DD-cxdl in Japan showed that responses were independent of CD25 expression, suggesting multiple mechanisms of action for DD-cxdl in MF/SS and potentially other malignancies.

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德尼白素对复发或难治性皮肤t细胞淋巴瘤治疗的评价。

摘要：Denileukin difitox （DD）是一种由全长人白细胞介素-2 （IL-2）结合白喉毒素a和B亚基组成的重组细胞毒融合蛋白，在肿瘤细胞表达CD25的复发和难治性（R/R）蕈样真菌病和Sezary综合征（MF/SS）患者中显示出活性，晚期和早期（I-III期）患者的有效率分别为30-44%。涵盖领域：最近开发了纯度和生物活性提高的新版本DD （DD-cxdl）。D-cxdl的注册试验显示，R/R MF/SS的缓解率相似。本综述的目的是描述这些药物的疗效和安全性数据，并强调这两种药物的等效性。专家意见：DD和DD-cxdl均在R/R MF/SS中表现出活性，在肿瘤和斑块期疾病中具有更高的应答率。不良事件≥3级包括8%的输液反应、22%的肝转氨酶升高和8%的毛细血管渗漏综合征。除了直接靶向表达CD25的肿瘤细胞外，这两种药物也能够消耗免疫调节性t细胞。日本的一项临床试验显示，DD-cxdl的应答不依赖于CD25的表达，这表明DD-cxdl在MF/SS和潜在的其他恶性肿瘤中具有多种作用机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Biological Therapy 医学-生物工程与应用微生物

CiteScore

8.60

自引率

0.00%

发文量

审稿时长

3-8 weeks

期刊介绍： Expert Opinion on Biological Therapy (1471-2598; 1744-7682) is a MEDLINE-indexed, international journal publishing peer-reviewed research across all aspects of biological therapy. Each article is structured to incorporate the author’s own expert opinion on the impact of the topic on research and clinical practice and the scope for future development. The audience consists of scientists and managers in the healthcare and biopharmaceutical industries and others closely involved in the development and application of biological therapies for the treatment of human disease. The journal welcomes: Reviews covering therapeutic antibodies and vaccines, peptides and proteins, gene therapies and gene transfer technologies, cell-based therapies and regenerative medicine Drug evaluations reviewing the clinical data on a particular biological agent Original research papers reporting the results of clinical investigations on biological agents and biotherapeutic-based studies with a strong link to clinical practice Comprehensive coverage in each review is complemented by the unique Expert Collection format and includes the following sections: Expert Opinion – a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results; Article Highlights – an executive summary of the author’s most critical points.