Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa

Abstract

Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings.

PD-L1/PD-1 expression and tumor-infiltrating lymphocytes in conjunctival melanoma

“…As far as we know, one ongoing clinical trial testing the efficacy and safety of Ipilimumab in metastatic melanoma patients is currently recruiting CM patients (NCT01355120). Very recently, a CM patient with a breast metastasis was successfully treated with Nivolumab, a monoclonal antibody directly against PD-1 [ 24 ]. However, the PD-L1 expression of the primary or metastatic tumor of the patient was not described.…”

HLA Class I Antigen Expression in Conjunctival Melanoma Is Not Associated With PD-L1/PD-1 Status

“…Very recently, Nivolumab (PD-1 inhibitor, Opdivo, Bristol-Myers Squibb, NY, USA) led to a successful clinical response in a CM patient with breast metastases. 21 However, effective T-cell immune responses also need a proper expression of the HLA class I antigens. Currently, very little is known regarding the expression of the HLA class I antigens in CM.…”

<p>Conjunctival Melanoma: Update on Genetics, Epigenetics and Targeted Molecular and Immune-Based Therapies</p>

“…103,104 Clinical application of immune checkpoint inhibitor therapy in the treatment of conjunctival melanoma has been reported in thirteen cases so far (Table 3). 34,37,39,[105][106][107] The clinical indication for treatment in the majority of cases was metastatic disease. 34,37,105,106 In four cases, checkpoint inhibitors were given for the management of locally advanced disease 37,107 and in one case both for locally advanced and metastatic disease.…”