Extracorporeal Photopheresis as a therapeutic approach for resistant immune-related adverse events in anti–PD-1-treated melanoma patients

Carl Maximilian Thielmann^1,2Johanna Andrea Seier¹Lisa Schielke¹Lea Jessica Albrecht¹Lisa Zimmer¹Elisabeth Livingstone¹Anne Zaremba^1,2Georg Christian Lodde^1,2Joachim Dissemond¹Wiebke Sondermann¹Frederik Krefting¹Alpaslan Tasdogan¹Alexander Roesch¹Eva Hadaschik¹Florian Rambow²Klaus Griewank¹Selma Ugurel³Dirk Schadendorf Schadendorf^1,4,5Jan-Malte Placke^1*

• ¹Essen University Hospital, Essen, Germany
• ²Universitatsklinikum Essen Institut fur kunstliche Intelligenz in der Medizin, Essen, Germany
• ³Department of Dermatology, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Bielefeld Rosenhöhe, Bielefeld, Germany
• ⁴Research Alliance Ruhr, Research Center One Health, University Duisburg-Essen, Campus Essen, Essen, Germany
• ⁵National Center for Tumor Diseases (NCT-West), Campus Essen, Essen, Germany

Background: Checkpoint inhibition induced immune-related adverse events (irAE) may be steroid-dependent or steroid-refractory and are associated with increased morbidity, mortality and potentially compromised anti-tumor immunity. Extracorporeal photopheresis (ECP) has emerged as an alternative for salvage therapy, however, evidence remains scarce. Methods: This monocenter retrospective study included patients with either irColitis or irHepatitis, who received ECP after failure or dependence on high-dose corticosteroids + infliximab/vedolizumab or mycophenolate mofetil/tacrolimus. Clinical activity was quantified at least weekly (stool frequency for colitis; AST/ALT for hepatitis) and primary endpoint was change in irAE activity over time. Secondary analyses included steroid-sparing, overall safety, and melanoma-specific outcomes. Spearman's correlation assessed irAE severity reduction. Results: Six patients were included in this study (irColitis n = 4; irHepatitis n = 2; CTCAE ≥ 3). Extracorporeal photopheresis was started after initial therapy with corticosteroids and immunosuppression was not successful. All ECP cycles included two consecutive treatment days. irAE activity declined promptly after ECP across patients: irColitis showed strong negative correlation with time since ECP (rs range -0.88 to -0.97); irHepatitis displayed parallel ALT/AST declines (rs ≥ -0.92). Corticosteroids were tapered following ECP start with a median corticosteroid reduction across all patients to 25% of baseline dose (IQR: 20.7 – 33.3) by week 4 and to <5% of baseline dose by week 9 (IQR: 1.6 – 4.7). No ECP-related adverse events were observed. Accelerated disease progression was not observed during or after ECP. Conclusions and Relevance: This study of six patients with irColitis or irHepatitis provides evidence that use of ECP is associated with clinical remission and steroid sparing, while demonstrating an excellent safety profile and not compromising disease control. Our data supports the use of ECP as salvage therapy for steroid-and immunosuppression-refractory irAE in cancer patients.