Kött Julian, Zell Tim, Zimmermann Noah, Rünger Alessandra, Smit Daniel J, Abeck Finn, Geidel Glenn, Hansen-Abeck Inga, Heidrich Isabel, Weichenthal Michael, Ugurel Selma, Leiter Ulrike, Berking Carola, Gutzmer Ralf, Schadendorf Dirk, Zimmer Lisa, Livingstone Elisabeth, Wasielewski Imke von, Mohr Peter, Meier Friedegund, Haferkamp Sebastian, Drexler Konstantin, Herbst Rudolf, Kellner Ivonne, Utikal Jochen, Wohlfeil Sebastian A, Pföhler Claudia, Adam Leonie, Terheyden Patrick, Ulrich Jens, Meiss Frank, Möbes Monica, Welzel Julia, Schilling Bastian, Ziller Fabian, Kaatz Martin, Kreuter Alexander, Sindrilaru Anca, Dippel Edgar, Sachse Michael, Weishaupt Carsten, Hüning Svea, Heinzerling Lucie, Loquai Carmen, Schley Gaston, Gambichler Thilo, Löffler Harald, Grabbe Stephan, Schultz Erwin, Devereux Nina, Hassel Jesscia C, Simon Jan-Ch, Raap Ulrike, Assaf Chalid, Klemke Claus-Detlev, Sunderkötter Cord, Hofmann Silke C, Wenk Saskia, Tronnier Michael, Thies Silke, Heppt Markus V, Eggermont Alexander, Schulze Hans-Joachim, Zouboulis Christos C, Tüting Thomas, Bauer Alexander T, Schneider Stefan W, Gebhardt Christoffer
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Eur J Cancer. 2025 Jan;214:115159. doi: 10.1016/j.ejca.2024.115159. Epub 2024 Nov 30.
Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent.
We examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS).
A significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301).
Our study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.
癌症免疫疗法彻底改变了黑色素瘤的治疗方式，但大量无反应者仍凸显出改进治疗方法的必要性。增强抗肿瘤治疗的一个潜在途径是通过调节凝血和血小板活性。二者均在肿瘤微环境、肿瘤生长和转移中发挥重要作用。临床前研究显示出有益效果，但临床数据并不一致。
我们研究了来自德国前瞻性多中心皮肤癌登记处ADOReg的一组晚期、不可切除的黑色素瘤患者（n = 2419），他们接受了免疫检查点抑制剂（ICI）治疗。根据是否记录到患者在ICI治疗开始时接受了血小板聚集抑制（PAI）（n = 137）（乙酰水杨酸（ASA）或氯吡格雷）、抗凝（AC）（n = 185）（直接口服抗凝剂（DOAC）、苯丙香豆素、肝素）或在ICI治疗期间的任何时间未接受抗血栓药物治疗（n = 2097），对患者进行分类。研究终点为最佳总体反应（BOR）、无进展生存期（PFS）和总生存期（OS）。
记录到接受ASA治疗的患者（15.1个月对6.4个月，HR 0.67，95%CI：0.5至0.88，p = 0.0047）以及接受AC治疗的患者（15.1个月对6.4个月，HR 0.7，95%CI：0.53至0.91，p = 0.01）的PFS与未记录抗血栓药物治疗的患者相比有显著改善。OS的多变量分析显示，接受DOAC治疗的患者（HR 0.68，95%CI：0.49至0.92，p = 0.0170）或苯丙香豆素治疗的患者（HR：0.44，95%CI：0.19至0.85，p = 0.0301）的风险显著降低。
我们的研究表明，在接受ICI治疗的黑色素瘤患者中，抗凝和抗血小板联合用药具有积极的预后效果。需要进一步研究来证实ICI治疗中添加抗凝或血小板抑制对癌症相关的益处。
