Department of Dermatology, Medical School, University Complutense, Hospital 12 de Octubre, Institute i+12, Madrid, Spain; CIBERONC, Madrid, Spain.
Department of Dermatology, Medical School, University Complutense, Hospital 12 de Octubre, Institute i+12, Madrid, Spain; CIBERONC, Madrid, Spain.
Lancet Haematol. 2022 Jun;9(6):e425-e433. doi: 10.1016/S2352-3026(22)00107-7.
The calcineurin pathway is often activated in mycosis fungoides. We aimed to assess the activity and safety of topical pimecrolimus, a calcineurin inhibitor, in patients with early mycosis fungoides.
PimTo-MF was a single-arm, multicentre, phase 2 trial done at six medical centres in Spain. Patients (aged ≥18 years) had histologically confirmed early mycosis fungoides (stages IA-IIA) and an Eastern Cooperative Oncology Group performance status of 0-1. Key exclusion criteria included the use of concurrent treatments for mycosis fungoides, including sunbathing, topical or systemic corticosteroids, and other calcineurin inhibitors. Patients applied topical pimecrolimus 1% cream on their skin lesions twice daily for 16 weeks (1 g per 2% of body surface), with subsequent follow-up of 12 months. Dosage modifications were not allowed. To evaluate adherence to the treatment, patients were instructed to return all empty tubes to the hospital (as per drug accountability protocols). The primary endpoint was the overall response ratein the intention-to-treat population. PimTo-MF is registered with EudraCT, 2014-001377-14, and is complete.
Between March 1, 2015, and Sept 30, 2016, 39 patients were enrolled. All patients were assessable, with a median age of 51·5 years (IQR 45-62), and the population was predominantly male (24 male [62%], 15 female [38%]). Median follow-up after baseline was 5·7 years (IQR 5·7-6·2). 22 (56%) of 39 patients had an overall response (one complete response, 21 partial responses). Responses were observed across IA (14 [54%] of 26 patients) and IB (eight [73%] of 11 patients) clinical stages, but not IIA. Topical pimecrolimus was well tolerated and no patient required a dose reduction or discontinued treatment because of unacceptable drug-related toxicity. No patients were lost to follow-up or discontinued treatment. 13 (33%) of 39 patients reported adverse events; transitory mild burning or pruritus (grade 1) was the most common, seen in eight (21%) patients. In three (8%) of these patients, the burning or pruritus was considered related to treatment. No grade 4 or 5 adverse events were observed.
Pimecrolimus 1% cream seems active and safe in patients with early stage mycosis fungoides. Our findings should be taken with caution until long-term follow-up data are obtained that confirm the safety of this treatment. Further controlled clinical trials are warranted to confirm these results.
Instituto de Salud Carlos III and the European Regional Development Fund.
For the Spanish translation of the abstract see Supplementary Materials section.
钙调磷酸酶通路在蕈样肉芽肿中常被激活。我们旨在评估钙调磷酸酶抑制剂他克莫司乳膏（pimecrolimus）治疗早期蕈样肉芽肿的活性和安全性。
PimTo-MF 是一项在西班牙六家医疗中心进行的单臂、多中心、二期临床试验。患者（年龄≥18 岁）有组织学证实的早期蕈样肉芽肿（IA-IIA 期）和东部合作肿瘤学组表现状态 0-1。主要排除标准包括同时使用其他治疗蕈样肉芽肿的药物，包括日光浴、局部或全身皮质类固醇和其他钙调磷酸酶抑制剂。患者每天两次在皮损处涂抹他克莫司乳膏 1%（每 2%的体表面积使用 1g），共 16 周，随后进行 12 个月的随访。不允许调整剂量。为了评估对治疗的依从性，要求患者将所有空管返回医院（根据药物核算协议）。主要终点是意向治疗人群的总缓解率。PimTo-MF 在 EudraCT 注册，注册号为 2014-001377-14，现已完成。
2015 年 3 月 1 日至 2016 年 9 月 30 日期间，共纳入 39 名患者。所有患者均可评估，中位年龄为 51.5 岁（IQR 45-62），人群中男性居多（24 名男性[62%]，15 名女性[38%]）。中位基线后随访时间为 5.7 年（IQR 5.7-6.2）。39 名患者中，22 名（56%）有总体缓解（完全缓解 1 例，部分缓解 21 例）。IA（26 例患者中的 14 例[54%]）和 IB（11 例患者中的 8 例[73%]）临床阶段均观察到缓解，但 IIA 期未见缓解。他克莫司乳膏耐受性良好，无患者因不可接受的药物相关毒性而需要减少剂量或停药。无患者失访或停药。39 名患者中有 13 名（33%）报告了不良事件；短暂的轻度灼热或瘙痒（1 级）最常见，8 名（21%）患者出现。在这 8 名患者中的 3 名（8%）中，灼热或瘙痒被认为与治疗有关。未观察到 4 级或 5 级不良事件。
他克莫司乳膏 1%乳膏在早期蕈样肉芽肿患者中似乎具有活性和安全性。在获得长期随访数据确认这种治疗的安全性之前，我们的发现应谨慎对待。需要进一步的对照临床试验来证实这些结果。
西班牙卡洛斯三世健康研究所和欧洲区域发展基金。
