Adoptive T-cell therapy achieved responses in 35% of patients with metastatic uveal melanoma.

  • Major finding: Adoptive T-cell therapy achieved responses in 35% of patients with metastatic uveal melanoma.

  • Clinical relevance: A subset of patients who were refractory to immune checkpoint blockade responded to T-cell therapy.

  • Impact: Autologous T-cell therapies warrant further investigation in patients with uveal melanoma.

There are no established treatments for metastatic uveal melanoma, and, to date, immunotherapies have had disappointing results despite their success in metastatic cutaneous melanoma. It has been suggested that uveal melanoma is resistant to immunotherapy, but adoptive T-cell therapies have not been investigated. Chandran and colleagues performed a single-arm phase II trial to evaluate the safety and efficacy of adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) in 21 patients with metastatic ocular melanoma. The patients underwent metastasectomies to obtain tissue for the generation of autologous TILs and were treated with chemotherapy to deplete lymphoid cells prior to autologous TIL infusion with high-dose IL2. The primary endpoint was objective tumor response. Secondary endpoints included toxicity and immunologic correlates of clinical response. Of the 20 evaluable patients, 7 (35%) achieved partial responses, 2 of which are ongoing, and one patient achieved a complete response of hepatic metastases. Three of the responding patients were refractory to previous therapy with immune checkpoint inhibitors, and 4 of the 7 responders harbored mutations in the BAP1 tumor suppressor gene. Grade 4 lymphopenia and neutropenia occurred in all 21 patients, and grade 3–4 thrombocytopenia occurred in all patients due to the lymphodepleting chemotherapy. There was one treatment-related death due to sepsis-induced multiorgan failure. Significant autoimmune adverse events were not observed. The results of this phase II trial suggest that metastatic uveal melanoma may not be resistant to immunotherapy, and support further refinement and investigation of T-cell therapy for the treatment of patients with uveal melanoma.

Chandran SS, Somerville RP, Yang JC, Sherry RM, Klebanoff CA, Goff SL, et al. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study. Lancet Oncol 2017 Apr 7 [Epub ahead of print].

Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.