MEK inhibitors combined with programmed cell death-1 blockade immunotherapy for metastatic uveal melanoma: is it warranted?

In the setting of metastatic uveal melanoma (mUM), prognosis is dismal and treatment options are limited. MEK inhibition using selumetinib has led to promising results with improved progression-free survival. While immune checkpoint inhibitors such as programmed cell death-1 (PD-1) blockade therapy (anti-PD-1) has shown discrete efficacy in mUM, combining MEK inhibitors (MEKi) to anti-PD-1 might be an option as such combinations have shown synergistic efficacy in metastatic cutaneous melanoma. We report here and discuss our experience in three patients who received this combination in the absence of suitable alternative treatment. The efficacy was difficult to assess due to early severe toxicities (pneumonitis and Takotsubo syndrome). This case series highlights the need to evaluate the safety and efficacy of new treatment options such as MEKi and anti-PD-1 for mUM.