Open Access

Julian Kött, Tim Zell, Noah Zimmermann, Alessandra Rünger, Daniel J. Smit, Finn Abeck, Glenn Geidel, Inga Hansen-Abeck, Isabel Heidrich, Michael Weichenthal, Selma Ugurel, Ulrike Leiter, Carola Berking, Ralf Gutzmer, Dirk Schadendorf, Lisa Zimmer, Elisabeth Livingstone, Imke von Wasielewski, Peter Mohr, Friedegund Meier, Sebastian Haferkamp, Konstantin Drexler, Rudolf Herbst, Ivonne Kellner, Jochen Utikal, Sebastian A. Wohlfeil, Claudia Pföhler, Leonie Adam, Patrick Terheyden, Jens Ulrich, Frank Meiss, Monica Möbes, Julia Welzel, Bastian Schilling, Fabian Ziller, Martin Kaatz, Alexander Kreuter, Anca Sindrilaru, Edgar Dippel, Michael Sachse, Carsten Weishaupt, Svea Hüning, Lucie Heinzerling, Carmen Loquai, Gaston Schley, Thilo Gambichler, Harald Löffler, Stephan Grabbe, Erwin Schultz, Nina Devereux, Jesscia C. Hassel, Jan-Ch. Simon, Ulrike Raap, Chalid Assaf, Claus-Detlev Klemke, Cord Sunderkötter, Silke C. Hofmann, Saskia Wenk, Michael Tronnier, Silke Thies, Markus V. Heppt, Alexander Eggermont, Hans-Joachim Schulze, Christos C. Zouboulis, Thomas Tüting, Alexander T. Bauer, Stefan W. Schneider, Christoffer Gebhardt

• Background 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. Methods 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 noBackground 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. Methods 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). Results 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). Conclusion 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.…