Abstract LB421: Extracorporeal photopheresis vs. systemic immunosuppression for treatment of immune-related adverse events: Final analysis of the prospective two-arm PRIA study

Abstract Purpose: Checkpoint inhibitor-induced immune-related adverse events (irAEs) can be steroid-refractory (sr) or steroid-dependent (sd), necessitating second-line therapy. This study compared extracorporeal photopheresis (ECP) with immunosuppressants (IS) in managing sr/sd-irAEs, balancing irAE mitigation with anti-tumor efficacy. Patients: This prospective, two-arm study analyzed 46 patients (23 ECP, 23 IS) with 12 distinct sr/sd-irAEs and five different tumor entities. Toxicities affected the gastrointestinal tract, skin, lung, musculoskeletal system, and serosal membranes, with up to seven prior treatment lines for irAEs. Patients underwent 12 weeks of either six cycles of ECP or investigator's choice IS, with longitudinal assessment of irAE outcome, quality of life (QoL), tumor response, and blood analyses. Results: At week 12, the ECP group exhibited a higher clinical irAE response rate (94% vs. 81%; p = 0.22), improved QoL scores (p = 0.01) and required significantly less steroids than the IS cohort with 437 mg vs. 1405 mg cumulative prednisolone equivalent, respectively (p = 0.02). ECP patients with advanced cutaneous melanoma showed superior overall survival (15 vs. 10 months; p = 0.02), longer progression-free survival (9 vs. 3 months; p = 0.01), and lower cancer progression rates (33% vs. 67%; p = 0.12) compared to the IS group. ECP was more frequently utilized in multi-toxicity cases (44% vs. 9%; p = 0.016) and in patients with prior second-line treatment refractoriness (39% vs. 17%; p = 0.19). No significant safety concerns were observed with ECP; one fatality in the IS group was linked to infection under immunosuppression. Conclusion: ECP demonstrates clinical superiority over IS in managing sr/sd-irAEs, with a favorable safety profile, and preserved anti-tumor response. A multicenter trial is planned for further investigation. Citation Format: Lisa Wein, Carolin Ertl, Theresa Ruf, Monika Morak, Ying Wang, Christina Schmitt, Xiomara Garza Vazquez, Valerie Glatzel, Richard David-Rus, Mohammed Mitwalli, Jerome Srour, Pia Schöpf, Dirk Tomsitz, Lars E. French, Lucie Heinzerling. Extracorporeal photopheresis vs. systemic immunosuppression for treatment of immune-related adverse events: Final analysis of the prospective two-arm PRIA study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB421.