Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma

J Immunother. 2017 Oct;40(8):307-311. doi: 10.1097/CJI.0000000000000181.

Abstract

Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis. Of note, both patients developed sarcoidosis only after undergoing immune checkpoint inhibitor therapy. In 1 patient, sarcoidosis developed after initiation of anti-PD-1 therapy, 3 months after the last dose of anti-CTLA-4 monotherapy, suggesting a synergistic immune dysmodulating effect of both checkpoint inhibitors. Ultimately, both patients' symptoms and radiologic findings resolved with corticosteroid treatment, and both patients have tolerated retreatment with PD-1 inhibitors. Sarcoidosis is a rare complication of immune checkpoint inhibitors and can manifest with severe pulmonary manifestations. However, sarcoidosis in this setting is responsive to corticosteroids and does not necessarily recur with retreatment. It is yet unclear whether the development of sarcoidosis in these patients represents unmasking of preexisting autoimmune tendencies or is a marker of oncologic response.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Autoimmunity
  • CTLA-4 Antigen / immunology
  • Drug-Related Side Effects and Adverse Reactions / diagnosis*
  • Female
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Ipilimumab / adverse effects
  • Ipilimumab / therapeutic use*
  • Lung / pathology
  • Melanoma / diagnosis*
  • Melanoma / drug therapy
  • Middle Aged
  • Nivolumab
  • Programmed Cell Death 1 Receptor / immunology
  • Sarcoidosis / diagnosis*
  • Sarcoidosis / etiology
  • Sarcoidosis / prevention & control
  • Skin / pathology
  • Skin Neoplasms / diagnosis*
  • Skin Neoplasms / drug therapy
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab