Immunotherapy With Programmed Cell Death 1 Inhibitors for 5 Patients With Conjunctival Melanoma

Abstract

onjunctival melanoma is a rare tumor with the potential to invade the eye, eyelid, and orbit and spread to regional lymphatics and distant sites, including the lungs, skin, liver, and brain. It was previously reported to have local recurrence rates of 36% to 45% at 5 years and 31% to 59% at 10 years. 1 Lymph node involvement was found in 19% of patients with conjunctival melanoma and systemic metastases were found in 19% of patients within 10 years after initial diagnosis. 1,2 Melanoma-related death was reported in 9% to 18% of patients at 5 years. [1][2][3] The mainstay of treatment for local control is surgical excision with margins clear of tumor; locally advanced disease may necessitate an orbital exenteration. Adjuvant treatments include topical chemotherapy and radiotherapy and are aimed at improving local control. Historically, treatment options for metastatic conjunctival melanoma have been limited.In recent years, immune checkpoint inhibitors, a new class of drugs, have been successfully used to treat metastatic cutaneous melanoma. Immune checkpoint inhibitors prevent cancer cells from activating mechanisms that enable the cells to evade the host's immune system. Immune checkpoint inhibitors, by blocking receptors on the surface of activated T lymphocytes, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), facilitate the recognition of cancer cells by lymphocytes and a consequent effective immune response. Ipilimumab (a CTLA-4 inhibitor), pembrolizumab (a PD-1 inhibitor), and nivolumab (a PD-1 inhibitor) are approved by the US Food and Drug Administration for the IMPORTANCE Conjunctival melanoma has the potential for regional lymphatic and distant metastasis. There is an urgent need for effective treatment for patients with metastatic or locally advanced conjunctival melanoma.OBJECTIVE To describe the use of immune checkpoint inhibitors for the treatment of conjunctival melanoma in 5 adult patients. DESIGN, SETTING, AND PARTICIPANTSA retrospective review was conducted of the medical records of 5 patients with conjunctival melanoma who were treated with immune checkpoint inhibitors from March 6, 2013, to July 7, 2017. MAIN OUTCOMES AND MEASURESResponse to treatment and disease-free survival. RESULTSOf the 5 patients (4 women and 1 man) with metastatic conjunctival melanoma, 4 were treated with a programmed cell death 1 (PD-1) inhibitor, nivolumab, and had a complete response to treatment with no evidence of disease at 1, 7, 9, and 36 months after completing treatment. One patient with metastatic conjunctival melanoma was treated with another PD-1 inhibitor, pembrolizumab, and had stable metastases during the first 6 months of treatment. Later disease progression resulted in treatment cessation after 11 months and switching to another therapy. Two patients treated with nivolumab developed autoimmune colitis that necessitated stopping the immunotherapy; these patients subsequently were managed with systemic corticosteroids or infliximab.CONCLUSIONS AND RELEVANCE This case ...

Orbital exenteration and conjunctival melanoma: a 14-year study at the Jules Gonin Eye Hospital

“…Prescribing these drugs as neoadjuvants may help surgeons to achieve free surgical margins and may reduce or eliminate micro-metastases. Also immunotherapy (anti-PD-1) could be a valid neoadjuvant therapy, since it has recently shown encouraging results in locally advanced and metastatic conjunctival melanoma [ 31 , 32 ].…”

Multicenter, International Assessment of the Eighth Edition of the American Joint Committee on Cancer Cancer Staging Manual for Conjunctival Melanoma

“…A small case series suggested that, like other mucous membrane melanomas, immunotherapy may be effective in the treatment of advanced local and metastatic conjunctival melanoma. 18 , 19 …”

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“…Sagiv et al, 2018). Notably, one of two patients with BRAF-mt CoM treated with a BRAF inhibitor in our institution responded well to treatment (unpublished).…”