Interleukin-2 and Interferon-alpha for Advanced Renal Cell Carcinoma: Patient Outcomes, Sexual Dimorphism of Responses, and Multimodal Treatment Approaches over a 30-Year Period

Introduction: Cytokine-based immunotherapy (IT) has been the mainstay of systemic treatment of advanced renal cell carcinoma (RCC) from the late 1980s until 2007. With the introduction of immune checkpoint inhibitors, a renaissance of immune oncological approaches is rapidly unfolding. Materials and Methods: In the present study, we revisited survival outcomes, sexual dimorphism of treatment responses, and the relevance of multimodal treatment approaches over a 30-year period in 156 patients with advanced RCC treated with subcutaneous (s.c.) interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) between 1990 and 2009. Results: The median progression-free survival following the first IT was 5.8 months with a wide range from 0 to 197 months. The median overall survival (OS) was 25.8 months and the median cancer-specific survival after tumor nephrectomy was 24.6 months. A group of 29 patients (18.6%) and 11 patients (7.1%) survived longer than 5 and 10 years after surgery, respectively. A difference in the 5-year OS rate between male and female patients was detected (men, 21.6%; women, 11.1%). However, no sex-specific survival advantage was observed after 10 years. Conclusions: We provide evidence that IT with s.c. IL-2 and IFN-alpha played a vital role in long-term survivors either by inducing lasting complete remissions or as part of multimodal approaches that allowed patients to survive until novel therapies became available. The implications for current immune oncological treatment approaches are being discussed. (C) 2022 S. Karger AG, Bas