Frontiers in Immunology (Jun 2024)

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

  • Elias A. T. Koch,
  • Elias A. T. Koch,
  • Elias A. T. Koch,
  • Elias A. T. Koch,
  • Anne Petzold,
  • Anne Petzold,
  • Anne Petzold,
  • Anne Petzold,
  • Edgar Dippel,
  • Michael Erdmann,
  • Michael Erdmann,
  • Michael Erdmann,
  • Michael Erdmann,
  • Anja Gesierich,
  • Ralf Gutzmer,
  • Jessica C. Hassel,
  • Sebastian Haferkamp,
  • Katharina C. Kähler,
  • Nicole Kreuzberg,
  • Ulrike Leiter,
  • Carmen Loquai,
  • Carmen Loquai,
  • Friedegund Meier,
  • Friedegund Meier,
  • Markus Meissner,
  • Peter Mohr,
  • Claudia Pföhler,
  • Farnaz Rahimi,
  • Beatrice Schell,
  • Patrick Terheyden,
  • Kai-Martin Thoms,
  • Selma Ugurel,
  • Jens Ulrich,
  • Jochen Utikal,
  • Jochen Utikal,
  • Michael Weichenthal,
  • Fabian Ziller,
  • Carola Berking,
  • Carola Berking,
  • Carola Berking,
  • Carola Berking,
  • Markus V. Heppt,
  • Markus V. Heppt,
  • Markus V. Heppt,
  • Markus V. Heppt

DOI
https://doi.org/10.3389/fimmu.2024.1395225
Journal volume & issue
Vol. 15

Abstract

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IntroductionDespite 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.MethodsIn 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).ResultsIn 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).ConclusionsThis 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.

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