Research in context
Evidence before this study
Before undertaking this study, we searched PubMed without date restrictions with the terms “metastatic uveal melanoma” and “immunotherapy” for articles published in any language. Although a variety of immune-based therapies have been efficacious in patients with metastatic cutaneous melanoma, their use in uveal melanoma has been disappointing. Recent reports evaluating immune checkpoint blockade therapy via anti-CTLA-4, anti-PD-1, and anti-PD-L1 have cumulatively shown limited efficacy in patients with metastatic uveal melanoma. These findings have led to speculation that melanomas arising from the uveal tract might be an immunotherapy-resistant variant. There are no published reports investigating the efficacy of adoptive transfer of tumour-infiltrating lymphocytes (TILs) in metastatic uveal melanoma.
Added value of this study
This report describes the largest cohort of patients with metastatic uveal melanoma treated with adoptive transfer of autologous TILs. An interim analysis of this ongoing trial found seven (35%) of 20 evaluable patients had objective tumour regression according to Response Evaluation Criteria in Solid Tumors. One patient achieved complete tumour regression of numerous hepatic metastases, currently ongoing at 21 months post therapy. To our knowledge, this is the first report of the use of TIL transfer to mediate objective tumour responses in patients with metastatic uveal melanoma, including individuals whose disease was refractory to immune checkpoint blockade.
Implications of all the available evidence
Adoptive T-cell therapy using autologous TILs has been reported to induce salvage responses in a variety of refractory solid tumours. This study now shows that this immunotherapeutic approach can also induce clinical responses in patients with metastatic uveal melanoma, a cancer that currently has no standard effective treatments. These initial findings challenge the belief that metastatic uveal melanoma is immunotherapy resistant and support the further investigation of immune-based therapies for this cancer.