Normalization of electroretinogram and symptom resolution of melanoma-associated retinopathy with negative autoantibodies after treatment with programmed death-1 (PD-1) inhibitors for metastatic melanoma

Cancer Immunol Immunother. 2021 Sep;70(9):2497-2502. doi: 10.1007/s00262-021-02875-x. Epub 2021 Feb 5.

Abstract

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome that involves the production of autoantibodies which can cross-react with retinal epitopes leading to visual symptoms. Autoantibodies can target intracellular proteins, and only a few are directed against membrane proteins. This discrepancy in autoantibody-protein target can translate into different immune responses (T-cell mediated vs B-cell mediated). Historically, treatment of MAR has focused on surgical reduction or immunosuppressive medication, mainly glucocorticoids. However, tumor resection is not relevant in metastatic melanoma in which MAR is mostly encountered. Moreover, the use of glucocorticoids can reduce the efficacy of immunotherapy. We report the first case to our knowledge with subjective resolution of visual symptoms and objective evidence of normalization of electroretinogram of MAR with undetectable autoantibodies after administration of programmed death-1 (PD-1) inhibitor (pembrolizumab) without the use of surgical reduction or systemic immunosuppression. This case highlights the potential improvement and resolution of negative autoantibody MAR with the use of PD-1 inhibitors and emphasizes the importance of multidisciplinary approach and team discussion to avoid interventions that can decrease immunotherapy-mediated anti-tumor effect.

Keywords: Autoantibodies; Melanoma-associated retinopathy; Metastatic melanoma; Paraneoplastic; Pembrolizumab; Programmed death-1 inhibitors.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Autoantibodies / immunology
  • Electroretinography* / methods
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Melanoma / complications*
  • Melanoma / drug therapy
  • Melanoma / etiology
  • Melanoma / pathology*
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Paraneoplastic Syndromes, Ocular / diagnosis*
  • Paraneoplastic Syndromes, Ocular / etiology*
  • Positron Emission Tomography Computed Tomography
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*

Substances

  • Autoantibodies
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor