PD-1 Inhibitors Effective in Metastatic Conjunctival Melanoma

A study published in JAMA Opthalmology has confirmed that PD-1 inhibitors, and nivolumab in particular, are effective in the treatment of metastatic conjunctival melanoma.

Conjunctival melanoma is a tumor that invades the eye and its surrounding regions and has the capability to spread towards other areas, such as the lung, skin, liver, and brain. First line treatment for local control involves surgical excision as well as adjuvant therapies such as topical chemotherapy and radiotherapy. Metastatic conjunctival melanoma, however, has had limited treatment options.

In a retrospective review, Sagiv et al sought to analyze response rates and disease-free survival among patients with metastatic conjunctival melanoma treated with checkpoint inhibitors.

Of the 5 patients whose outcomes were analyzed, 4 were treated with nivolumab while 1 was treated with pembrolizumab. All patients presented with metastatic conjunctival melanoma, primarily to the lungs.

The first patient, a white 58-year-old woman, received nivolumab 3 mg/kg every 2 weeks. The patient received treatment for 3 months and discontinued treatment due to elevated liver enzyme levels. At 9 months, the patient had complete resolution of metastatic lesions, with no evidence of disease on imaging scans or clinical examination.

Patient 2 was a younger woman in her 20s, whose metastatic melanoma was confirmed through presentation of a mass in her right breast. The patient received nivolumab 3 mg/kg every 2 weeks for 7 cycles. After 3.5 months, the patient also achieved a complete response and remained disease free 3 years after completion of nivolumab treatment.

The remaining 3 patients presented with similar cases of metastatic conjunctival metastasis spreading towards the lungs. Patient 3 received nivolumab 3 mg/kg every 2 weeks and had a complete resolution of her lung metastasis after 4 cycles of treatment. After 5 months of treatment, the patient developed drug-induced autoimmune colitis, which was controlled with prednisone and infliximab. At 7 months after discontinuation of nivolumab, the patient was still disease-free.

Patient 5 experienced similar immune-related colitis after 11 months of treatment with nivolumab. One month after discontinuing nivolumab, the patient presented with no evidence of distant metastasis.

Patient 4 was the only one to be treated with pembrolizumab instead of nivolumab. The patient was stable for 6 months of treatment; however, disease progression was documented at the 11-month follow-up and pembrolizumab was discontinued. The patient was switched to ipilimumab with dacarbazine, but treatment was discontinued after 2 cycles of treatment because of grade 4 hepatoxicity.

Based on this analysis, investigators concluded that anti—PD-1 checkpoint inhibitors, particularly nivolumab, offer substantial clinical benefits in patients with metastatic cutaneous melanoma.

Reference

Sagiv O, Thakar SD, Kandl TJ, et al. Immunotherapy with programmed cell death 1 inhibitors for 5 patients with conjunctival melanoma [published online August 23, 2018]. JAMA Ophthalmol. doi: 10.1001/jamaophthalmol.2018.3488.