Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis

Cancer Immunol Res. 2014 Jan;2(1):15-8. doi: 10.1158/2326-6066.CIR-13-0146. Epub 2013 Oct 7.

Abstract

Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • CTLA-4 Antigen / antagonists & inhibitors
  • Humans
  • Hypothyroidism / diagnosis
  • Hypothyroidism / etiology
  • Ipilimumab
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology*
  • Middle Aged
  • Mucous Membrane / pathology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Rhabdomyolysis / diagnosis
  • Rhabdomyolysis / etiology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • CTLA-4 Antigen
  • Ipilimumab
  • Programmed Cell Death 1 Receptor
  • pembrolizumab