Stadler Rudolf, Roccuzzo Gabriele, Ortiz-Romero Pablo, Bagot Martine, Quaglino Pietro, Guenova Emmanuella, Jonak Constanze, Papadavid Evangelia, Stranzenbach René, Marreaud Sandrine, Musoro Jammbe, Casas-Martin Jose, Murray Duncan, Drennan Samantha, Hear Jimmy Van, Moss Paul, Sartori Delphine, Battistella Maxime, Willemze Rein, Scarisbrick Julia, Knobler Robert
University Clinic for Dermatology, Ruhr University of Bochum, Minden, Germany.
Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy.
Eur J Cancer. 2025 Jun 3;222:115484. doi: 10.1016/j.ejca.2025.115484. Epub 2025 Apr 30.
Treatment of advanced mycosis fungoides (MF) and Sézary syndrome (SS) is a challenge. In this international, multicenter, open-label phase II trial, we assessed the efficacy and safety of anti-PD-L1 atezolizumab in stage IIB-IV refractory/relapsed MF and SS.
Patients received atezolizumab 1200 mg IV Q3w for up to 1 year unless progression or withdrawal. The main study endpoints were overall response rate (ORR), progression-free survival (PFS), time to next systemic treatment (TTNT), and overall survival (OS).
A total of 26 patients were enrolled from seven countries. Seventeen patients met the inclusion criteria. At a median follow-up of 36.6 months, the ORR was 15.4 % in the intention to treat (ITT) and 17.6 % in the per protocol (PP) population, respectively. In the PP group, 58.8 % of patients, and in the ITT group, 53.9 % of patients achieved partial response or stable disease as their best outcome. One complete response was observed after 1 year. Median PFS was 3 months (95 % CI 1.4-4.9) in PP and 3.1 months (95 % CI 2.4-4.0) in ITT. Median OS was not reached for PP and was 22.3 months (20.0-NE) for ITT. Median TTNT was 5.9 months (2.8-NE) in PP and 6.2 months (3.1-14.8) in ITT. The most common grade ≥ 3 adverse events were fatigue (23.1 %) and infections (15.4 %), with two sepsis-related deaths. Atezolizumab was primarily discontinued due to disease progression (50 %).
Atezolizumab shows moderate activity in pretreated refractory/relapsed MF and SS. Further studies are needed to identify reliable predictors of safety and treatment response.
晚期蕈样肉芽肿（MF）和塞扎里综合征（SS）的治疗是一项挑战。在这项国际多中心、开放标签的II期试验中，我们评估了抗程序性死亡受体配体1（PD-L1）阿特珠单抗在IIB-IV期难治性/复发性MF和SS中的疗效和安全性。
患者接受阿特珠单抗1200mg静脉注射，每3周一次，最长1年，除非病情进展或退出试验。主要研究终点为总缓解率（ORR）、无进展生存期（PFS）、至下次全身治疗时间（TTNT）和总生存期（OS）。
共从7个国家招募了26例患者。17例患者符合纳入标准。中位随访36.6个月时，意向性分析（ITT）人群的ORR为15.4%，符合方案（PP）人群的ORR为17.6%。在PP组中，58.8%的患者以及在ITT组中，53.9%的患者达到部分缓解或疾病稳定作为最佳转归。1年后观察到1例完全缓解。PP组的中位PFS为3个月（95%CI 1.4-4.9），ITT组为3.1个月（95%CI 2.4-4.0）。PP组未达到中位OS，ITT组为22.3个月（20.0-未达到）。PP组的中位TTNT为5.9个月（2.8-未达到），ITT组为6.2个月（3.1-14.8）。最常见的≥3级不良事件为疲劳（23.1%）和感染（15.4%），有2例与脓毒症相关的死亡。阿特珠单抗主要因疾病进展（50%）而停用。
阿特珠单抗在预处理的难治性/复发性MF和SS中显示出中等活性。需要进一步研究以确定安全性和治疗反应的可靠预测指标。
