Surveillance of the eye and vision in clinical trials of CP-675,206 for metastatic melanoma

Am J Ophthalmol. 2007 Jun;143(6):958-969. doi: 10.1016/j.ajo.2007.02.035. Epub 2007 Apr 16.

Abstract

Purpose: To determine the ocular safety of CP-675,206 (Pfizer, New York, New York, USA), a fully human anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody in clinical trials of immunotherapy of metastatic melanoma.

Design: Prospective, nonrandomized study of the eye and vision in phase I/II clinical trials of CP-675,206 in metastatic melanoma conducted at the University of California, Los Angeles.

Methods: Patients with regional or distant metastatic melanoma were enrolled in phase I/II clinical trials evaluating the safety and antitumor efficacy of CP-675,206 alone or in combination with melanoma antigen peptide-pulsed dendritic cell vaccines. Ophthalmic evaluation was performed at the onset of CP-675,206 immunotherapy (baseline evaluation), two months or more after the onset of CP-675,206 immunotherapy (end-study evaluation), and at two- to three-month intervals thereafter in patients who continued to receive CP-675,206 immunotherapy (poststudy evaluation). Baseline and end-study evaluations included comprehensive ophthalmic examination, psychophysical and electrophysiologic visual function assessment, fundus photography, fluorescein angiography, and visual function assessment.

Results: Twenty patients with metastatic melanoma arising from the skin, mucosa, eye, or unknown site were evaluated. Systemic toxicity attributed to CP-675,206 included dermatologic manifestations, diarrhea, and autoimmune hepatitis with panhypopituitarism. A subset of patients receiving CP-675,206 demonstrated antitumor efficacy with partial response or complete response of metastatic melanoma. Comparison of ophthalmic baseline with end-study evaluations in all 20 patients and limited-term poststudy evaluations showed no adverse effect of CP-675,206 immunotherapy on the eye or vision.

Conclusions: In this study, CP-675,206 immunotherapy for metastatic melanoma did not adversely affect the eye or vision.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abatacept
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Blocking / adverse effects
  • Antibodies, Blocking / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm / immunology
  • Anus Neoplasms / pathology
  • Anus Neoplasms / therapy
  • Choroid Neoplasms / pathology
  • Choroid Neoplasms / therapy
  • Drug Therapy, Combination
  • Electrooculography
  • Electroretinography
  • Female
  • Fluorescein Angiography
  • Humans
  • Immunoconjugates / immunology*
  • Immunotherapy*
  • MART-1 Antigen
  • Male
  • Melanoma / secondary
  • Melanoma / therapy*
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Ocular Physiological Phenomena*
  • Prospective Studies
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • Treatment Outcome
  • Vision, Ocular / physiology*
  • Visual Acuity

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Immunoconjugates
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Abatacept
  • tremelimumab