Ocular and systemic autoimmunity after successful tumor-infiltrating lymphocyte immunotherapy for recurrent, metastatic melanoma.

Abstract

OBJECTIVE:

To describe the ophthalmic and systemic autoimmune findings after successful adoptive cell transfer of ex vivo expanded, autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) for metastatic melanoma.

DESIGN:

Retrospective, interventional case report.

PARTICIPANT:

A 35-year-old man who underwent immunotherapy for metastatic melanoma with adoptive cell transfer of tumor-reactive TIL.

METHODS:

A 35-year-old man with metastatic melanoma was treated with TIL plus interleukin-2 (IL-2) therapy after a lymphodepleting regimen of cyclophosphamide and fludarabine for metastatic melanoma, which led to a complete and durable remission. Bilateral panuveitis, hearing loss, vitiligo, poliosis, and alopecia developed in the patient, requiring local ophthalmic immunosuppressive therapy. The clinical course, diagnostic testing, and therapeutic interventions over a 2-year period are reviewed.

MAIN OUTCOME MEASURES:

Visual acuity, anterior chamber and vitreous inflammation, optical coherence tomography findings, serial electro-oculograms (EOGs), microperimetry (MP-1) testing, flow cytometric analysis of cells derived from the aqueous humor, and aqueous humor cytokine profiles were evaluated.

RESULTS:

After melanoma immunotherapy, complete tumor regression was achieved at 5 months after treatment with a durable, ongoing, complete remission at 24 months. Early in the treatment course, a high fever, a diffuse rash, hearing loss, and bilateral anterior uveitis developed acutely in the patient. Late autoimmune sequelae included the development of alopecia, vitiligo, poliosis, and bilateral panuveitis with diffuse retinal pigment epithelium (RPE) hypopigmentation, reminiscent of Vogt-Koyanagi-Harada (VKH) syndrome. Bilateral cystoid macular edema also developed that was responsive to acetazolamide. Serial EOGs showed alterations in RPE standing potentials in dark conditions, and MP-1 testing revealed diminished foveal and perifoveal sensitivity. An aqueous humor aspirate revealed a high concentration of melanoma tumor antigen-reactive T cells compared with that of peripheral blood samples, as well as a proinflammatory aqueous cytokine profile. At the time of cataract surgery 22 months after immunotherapy, a repeat aqueous humor sample showed the disappearance of the previously seen melanoma differentiation antigen-reactive lymphocytes, but the proinflammatory cytokine profile persisted.

CONCLUSIONS:

Ocular and systemic autoimmune sequelae resembling VKH may develop after successful melanoma immunotherapy. This report provides insight into the pathogenesis of VKH disease. The patient's clinical course illustrates the fine balance between tumor-specific immunity and loss of self-tolerance.

FINANCIAL DISCLOSURE(S):

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

• Authors: Steven Yeh, Neel K Karne, Sid P Kerkar, Charles K Heller, Douglas C Palmer, Laura A Johnson, Zhuqing Li, Rachel J Bishop, Wai T Wong, Richard M Sherry, James C Yang, Mark E Dudley, Nicholas P Restifo, Steven A Rosenberg, Robert B Nussenblatt
• Journal: Ophthalmology (Ophthalmology) Vol. 116 Issue 5 Pg. 981-989.e1 (May 2009) ISSN: 1549-4713 [Electronic] United States
• PMID: 19410956 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cytokines
• Interleukin-2
• Melanoma-Specific Antigens
• Neoplasm Proteins

Topics

• Adult
• Antigens, Neoplasm (immunology)
• Aqueous Humor (cytology, metabolism)
• Autoimmunity
• Colonic Neoplasms (immunology, secondary, therapy)
• Cytokines (metabolism)
• Electrooculography
• Flow Cytometry
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Interleukin-2 (therapeutic use)
• Lymphatic Metastasis
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Melanoma (immunology, secondary, therapy)
• Melanoma-Specific Antigens
• Neoplasm Proteins (immunology)
• Neoplasm Recurrence, Local (immunology, therapy)
• Retrospective Studies
• Tomography, Optical Coherence
• Uveomeningoencephalitic Syndrome (etiology, immunology)
• Visual Field Tests