Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis

被引:70
作者
Heppt, Markus V. [1 ]
Eigentler, Thomas K. [2 ]
Kaehler, Katharina C. [3 ]
Herbst, Rudolf A. [4 ]
Goeppner, Daniela [5 ]
Gambichler, Thilo [6 ]
Ulrich, Jens [7 ]
Dippel, Edgar [8 ]
Loquai, Carmen [9 ]
Schell, Beatrice [10 ]
Schilling, Bastian [11 ,12 ]
Schaed, Susanne G. [13 ]
Schultz, Erwin S. [14 ]
Matheis, Fanny [1 ]
Tietze, Julia K. [1 ]
Berking, Carola [1 ]
机构
[1] Munich Univ Hosp LMU, Dept Dermatol & Allergy, Frauenlobstr 9-11, D-80337 Munich, Germany
[2] Univ Tubingen Hosp, Dept Dermatol, Ctr Dermatooncol, Liebermeisterstr 25, D-72076 Tubingen, Germany
[3] Univ Hosp Schleswig Holstein, Dept Dermatol, Campus Kiel,Schittenhelmstr 7, D-24105 Kiel, Germany
[4] HELIOS Clin Erfurt, HELIOS Skin Canc Ctr Erfurt, Nordhauser Str 74, D-99089 Erfurt, Germany
[5] Otto von Guericke Univ Hosp, Dept Dermatol & Venereol, Leipziger Str 44, D-39120 Magdeburg, Germany
[6] Ruhr Univ Bochum, Dept Dermatol, Skin Canc Ctr, Gudrunstr 56, D-44791 Bochum, Germany
[7] Harzklinikum Dorothea Christiane Erxleben, Dept Dermatol, Ditfurter Weg 24, D-06484 Quedlinburg, Germany
[8] Clin Ctr Ludwigshafen, Dept Dermatol, Bremserstr 79, D-67073 Ludwigshafen, Germany
[9] Univ Med Ctr Mainz, Dept Dermatol, Langenbeckstr 1, D-55131 Mainz, Germany
[10] SRH Wald Klinikum Gera GmbH, Dept Dermatol, Str Friedens 122, D-07548 Gera, Germany
[11] Univ Duisburg Essen, Univ Hosp, Dept Dermatol, Hufelandstr 55, D-45122 Essen, Germany
[12] German Canc Consortium DKTK, Heidelberg, Germany
[13] Univ Med Ctr Rostock, Dept Dermatol & Venereol, Strempelstr 13, D-18057 Rostock, Germany
[14] Paracelsus Med Univ, Gen Hosp Nuremberg, Dept Dermatol, Prof Ernst Nathan Str 1, D-90419 Nurnberg, Germany
关键词
Electrochemotherapy; Ipilimumab; Pembrolizumab; Nivolumab; Melanoma; Immune checkpoint blockade; UNTREATED MELANOMA; METASTATIC MELANOMA; COMBINED NIVOLUMAB; IPILIMUMAB; PEMBROLIZUMAB; CHEMOTHERAPY; MONOTHERAPY; TUMORS; TRIAL;
D O I
10.1007/s00262-016-1856-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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收藏
页码:951 / 959
页数:9
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