Optimizing immune checkpoint blockade in metastatic uveal melanoma: exploring the association of overall survival and the occurrence of adverse events

• Published in: Frontiers in immunology Vol. 15; p. 1395225
• Main Authors: Koch, Elias A. T., Petzold, Anne, Dippel, Edgar, Erdmann, Michael, Gesierich, Anja, Gutzmer, Ralf, Hassel, Jessica C., Haferkamp, Sebastian, Kähler, Katharina C., Kreuzberg, Nicole, Leiter, Ulrike, Loquai, Carmen, Meier, Friedegund, Meissner, Markus, Mohr, Peter, Pföhler, Claudia, Rahimi, Farnaz, Schell, Beatrice, Terheyden, Patrick, Thoms, Kai-Martin, Ugurel, Selma, Ulrich, Jens, Utikal, Jochen, Weichenthal, Michael, Ziller, Fabian, Berking, Carola, Heppt, Markus V.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 10.06.2024
• Subjects: Adult; adverse events; Aged; Aged, 80 and over; CTLA-4; Female; Humans; immune checkpoint blockade; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; immune-related; Immunology; Male; Melanoma - drug therapy; Melanoma - immunology; Melanoma - mortality; Middle Aged; Neoplasm Metastasis; PD-1; uveal melanoma; Uveal Neoplasms - drug therapy; Uveal Neoplasms - immunology; Uveal Neoplasms - mortality; Uveal Neoplasms - pathology; toxicity; uveal melanoma; CTLA-4; adverse events; immune-related; PD-1; immune checkpoint blockade
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1395225

Despite recent advancements in the treatment of metastatic uveal melanoma (UM), the availability of further treatment options remains limited and the prognosis continues to be poor in many cases. In addition to tebentafusp, immune checkpoint blockade (ICB, PD-1 (+/-) CTLA-4 antibodies) is commonly used for metastatic UM, in particular in HLA-A 02:01-negative patients. However, ICB comes at the cost of potentially severe immune-related adverse events (irAE). Thus, the selection of patient groups that are more likely to benefit from ICB is desirable. In this analysis, 194 patients with metastatic UM undergoing ICB were included. Patients were recruited from German skin cancer sites and the ADOReg registry. To investigate the association of irAE occurrence with treatment response, progression-free survival (PFS), and overall survival (OS) two cohorts were compared: patients without irAE or grade 1/2 irAE (n=137) and patients with grade 3/4 irAE (n=57). In the entire population, the median OS was 16.4 months, and the median PFS was 2.8 months. Patients with grade 3/4 irAE showed more favorable survival than patients without or grade 1/2 irAE (p=0.0071). IrAE occurred in 44.7% (87/194), and severe irAE in 29.4% (57/194) of patients. Interestingly, irColitis and irHepatitis were significantly associated with longer OS (p=0.0031 and p=0.011, respectively). This data may indicate an association between irAE and favorable survival outcomes in patients with metastatic UM undergoing ICB treatment and suggests that a reduced tolerance to tumor antigens could be linked to reduced tolerance to self-antigens.