Heppt Markus V, Eigentler Thomas K, Kähler Katharina C, Herbst Rudolf A, Göppner Daniela, Gambichler Thilo, Ulrich Jens, Dippel Edgar, Loquai Carmen, Schell Beatrice, Schilling Bastian, Schäd Susanne G, Schultz Erwin S, Matheis Fanny, Tietze Julia K, Berking Carola
Department of Dermatology and Allergy, Munich University Hospital (LMU), Frauenlobstr. 9-11, 80337, Munich, Germany.
Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany.
Cancer Immunol Immunother. 2016 Aug;65(8):951-9. doi: 10.1007/s00262-016-1856-z. Epub 2016 Jun 13.
Growing evidence suggests that concurrent loco-regional and systemic treatment modalities may lead to synergistic anti-tumor effects in advanced melanoma. In this retrospective multicenter study, we evaluate the use of electrochemotherapy (ECT) combined with ipilimumab or PD-1 inhibition. We investigated patients with unresectable or metastatic melanoma who received the combination of ECT and immune checkpoint blockade for distant or cutaneous metastases within 4 weeks. Clinical and laboratory data were collected and analyzed with respect to safety and efficacy. A total of 33 patients from 13 centers were identified with a median follow-up time of 9 months. Twenty-eight patients received ipilimumab, while five patients were treated with a PD-1 inhibitor (pembrolizumab n = 3, nivolumab n = 2). The local overall response rate (ORR) was 66.7 %. The systemic ORR was 19.2 and 40.0 % in the ipilimumab and PD-1 cohort, respectively. The median duration of response was not reached in either group. The median time to disease progression was 2.5 months for the entire population with 2 months for ipilimumab and 5 months for PD-1 blockade. The median overall survival was not reached in patients with ipilimumab and 15 months in the PD-1 group. Severe systemic adverse events were detected in 25.0 % in the ipilimumab group. No treatment-related deaths were observed. This is the first reported evaluation of ECT and simultaneous PD-1 inhibition and the largest published dataset on ECT with concurrent ipilimumab. The local response was lower than reported for ECT only. Ipilimumab combined with ECT was feasible, tolerable and showed a high systemic response rate.
越来越多的证据表明，局部区域和全身联合治疗模式可能会在晚期黑色素瘤中产生协同抗肿瘤作用。在这项回顾性多中心研究中，我们评估了电化学疗法（ECT）联合伊匹单抗或PD-1抑制剂的应用。我们调查了在4周内接受ECT与免疫检查点阻断联合治疗远处或皮肤转移的不可切除或转移性黑色素瘤患者。收集并分析了关于安全性和疗效的临床及实验室数据。共确定了来自13个中心的33例患者，中位随访时间为9个月。28例患者接受了伊匹单抗治疗，而5例患者接受了PD-1抑制剂治疗（帕博利珠单抗n = 3，纳武利尤单抗n = 2）。局部总缓解率（ORR）为66.7%。伊匹单抗组和PD-1队列的全身ORR分别为19.2%和40.0%。两组均未达到中位缓解持续时间。整个人群的疾病进展中位时间为2.5个月，伊匹单抗组为2个月，PD-1阻断组为5个月。伊匹单抗组患者未达到中位总生存期，PD-1组为15个月。伊匹单抗组有25.0%的患者出现严重的全身不良事件。未观察到与治疗相关的死亡。这是首次报道的ECT与同时进行的PD-1抑制的评估，也是关于ECT联合伊匹单抗的最大已发表数据集。局部反应低于仅报道的ECT。伊匹单抗联合ECT是可行的、可耐受的，且显示出较高的全身反应率。
