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Verdinexor治疗初治犬皮肤亲上皮性T细胞淋巴瘤的疗效:一项开放标签的试点研究。

Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study.

作者信息

Vlodaver Elana M, Keating M Kelly, Bidot Willie A, Bruyette David S, Rosenkrantz Wayne S

机构信息

Animal Dermatology Group Inc, Tustin, California, USA.

Animal Dermatology Group Inc, Las Vegas, Nevada, USA.

出版信息

Vet Dermatol. 2024 Oct;35(5):536-546. doi: 10.1111/vde.13280. Epub 2024 Jul 29.

Abstract

BACKGROUND

Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL).

HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of verdinexor for the treatment of CETL.

ANIMALS

Eight client-owned animals with CETL.

MATERIALS AND METHODS

Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days).

RESULTS

Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy.

CONCLUSIONS AND CLINICAL RELEVANCE

Verdinexor could be considered a safe, palliative treatment for canine CETL.

摘要

背景

Verdinexor(Laverdia - CA1;Dechra兽用产品公司),一种核输出的选择性抑制剂,已被用于治疗犬非霍奇金T细胞淋巴瘤。然而,Verdinexor对皮肤亲上皮性T细胞淋巴瘤(CETL)的疗效尚未得到评估。

假设/目的:评估Verdinexor治疗CETL的疗效。

动物

8只患有CETL的客户拥有的动物。

材料与方法

患者每周口服两次Verdinexor,剂量为1.28至1.45mg/kg,两次给药间隔至少72小时,直至疾病进展或自愿停药。在第14天(D14)后允许使用洛维单抗或泼尼松进行辅助治疗。每14天评估一次临床病变(犬实体瘤反应评估标准[cRECIST v1.0]和新的犬亲上皮性淋巴瘤范围和严重程度指数[CELESI])、瘙痒(视觉模拟量表)和治疗效果(主人对治疗效果的整体评估[OGATE]),持续3个月,此后每月评估一次(平均70±43.4天)。

结果

75%的患者达到完全缓解、部分缓解或疾病稳定。疾病进展的平均时间为56±41天。将每只犬的最低CELESI评分与其在D0时的评分进行比较时,总CELESI评分有显著降低(p = 0.026)。Verdinexor在任何时间点都未显著减轻瘙痒(p = 0.45),包括单药治疗或与洛维单抗±糖皮质激素联合使用时。在D28时,75%的主人将治疗反应评为“一般”至“优秀”。最常见的不良反应包括体重减轻、食欲不振、呕吐和嗜睡。

结论及临床意义

Verdinexor可被视为犬CETL的一种安全的姑息治疗方法。

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