Checkpoint inhibition immunotherapy for advanced local and systemic conjunctival melanoma: a clinical case series

Abstract

Background: Herein, we describe the use of systemic immunotherapy for both locally advanced and metastatic conjunctival melanoma. Current treatments for advanced conjunctival melanoma typically result in poor local control leading to disfiguring orbital exenteration surgery. Locoregional spread of conjunctival malignant melanoma typically requires pre-auricular and cervical lymph node dissection with post-operative adjuvant radiation therapy. In addition, classic systemic chemotherapy has been unsuccessful in the treatment of metastatic disease.

Methods: This is a retrospectively analyzed clinical case series of 5 patients with biopsy proven conjunctival melanoma who were treated with checkpoint inhibition therapy. Of these, 3 patients were treated for residual ocular disease present after failing multiple local therapies and refusing orbital exenteration surgery and two (with local ocular control) for metastatic conjunctival melanoma. Both those with locally advanced disease and patients with metastatic disease received an anti-PD1 agent in combination with another immunotherapeutic agent. All 5 were given multiple cycles of systemic anti-PD1 therapy, 1 was initially treated with single agent ipilimumab (3 mg/kg) prior to approval of anti-PD1 agents and two received interferon eye drops. As part of each ophthalmic examination, photographs of all conjunctival and eyelid surfaces were obtained. Systemic evaluations involved initial staging scans as well as periodic re-imaging.

Results: All cases have shown responses. Of the 2 complete responses, 1 was a patient with systemic disease. No patients developed ocular toxicity or loss of vision. However, systemic adverse effects included adrenal insufficiency, Grade-III colitis, Grade-II dermatitis, Grade-II hepatotoxicity and Grade-II pneumonitis.

Conclusions: This report suggests that systemic immunotherapy with or without topical interferon is effective in treatment of malignant melanoma of the conjunctiva. Therefore, it can be considered for patients with advanced local conjunctival melanoma, those who refuse orbital exenteration surgery and those with systemic metastasis.

Keywords: Checkpoint; Conjunctiva; Immunotherapy; Interferon; Ipilimumab; Melanoma; Metastasis; Nivolumab; Pembrolizumab; Topical.

Fig. 1

Top, 4 photographic images demonstrating the extent of local bulbar and palpebral conjunctival melanoma prior to systemic immunotherapy. Bottom 3 years later, 4-photographic images demonstrate the extent of regression after combination systemic and topical chemotherapy. Please note that the top 4 images (below the blue line) correspond to the bottom 4 images as before and after photographs. For example, the top left image, of the top 4 images corresponds to the top left of the bottom 4 images

Fig. 2

Top 4-up images, Patient #5, note the contrast enhanced, transverse abdominal computed tomography (CT) reveal a large solitary CMM metastasis on 2/2016, 7/2016, 4/2017 and 10/18 respectively (arrows). Middle 4-up CT-images reveal two additional CMM metastases on 2/2016, 7/2016, 2//2017 and 10/2018 respectively. Bottom 4-up CT images of a 2.7 mm abdominal implant prior to treatment on 2/2016, 7/2016, 4/2017 and 10/2018 where resolution is noted