Metastatic Uveal Melanoma Response to Adoptive Transfer of Autologous Tumor-Infiltrating Lymphocytes
As reported by Chandran et al in The Lancet Oncology, a single-center study has shown that adoptive transfer of autologous tumor-infiltrating lymphocytes produces tumor responses in metastatic uveal melanoma.
Study Details
The study involved 21 consecutive patients treated at the Surgery Branch of the National Cancer Institute. Autologous tumor-infiltrating lymphocyte cultures were generated from tumor tissue obtained from metastasectomies and underwent large-scale ex vivo expansion.
Lymphodepleting conditioning chemotherapy consisted of cyclophosphamide at 60 mg/kg daily for 2 days followed by fludarabine at 25 mg/m² daily for 5 days and a single intravenous infusion of autologous tumor-infiltrating lymphocytes and high-dose interleukin-2 (720,000 IU/kg) every 8 hours. The study is ongoing, with the current report providing findings in a completed first stage and ongoing expansion stage.
Responses
Objective response occurred in 7 of 20 evaluable patients (35%, 95% confidence interval [CI] = 16%–59%). Of six patients with partial response, two have ongoing responses that had not reached maximum response at the time of analysis; response durations were 3 to 9 months in the other four patients. One patient showed complete response of numerous hepatic metastases, with the response ongoing at 21 months. In responders, tumor regression was observed at numerous sites, including extrahepatic and hepatic metastases. Five responders had received at least three regimens for metastatic disease, with no response; three of these patients had progressed after both cytotoxic T-lymphocyte–associated protein 4 and programmed cell death protein 1 immune checkpoint inhibitor therapy.
Toxicity
Grade ≥ 3 toxicity was related to the lymphodepleting regimen, including lymphopenia, neutropenia, and thrombocytopenia in all 21 patients (100%), anemia in 67%, and infection in 29%. One patient died of treatment-related sepsis-induced multiorgan failure.
The investigators concluded: “To our knowledge, this is the first report describing adoptive transfer of autologous [tumor-infiltrating lymphocytes] to mediate objective tumour regression in patients with metastatic uveal melanoma. These initial results challenge the belief that metastatic uveal melanoma is immunotherapy resistant and support the further investigation of immune-based therapies for this cancer. Refinement of this T-cell therapy is crucial to improve the frequency of clinical responses and the general applicability of this treatment modality.”
The study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute.
Udai S. Kammula, MD, of the Center for Cancer Research, National Cancer Institute, is the corresponding author of The Lancet Oncology article.
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