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Adoptive cell therapy associated with complete, durable regression of melanoma brain metastases
Hong JJ. Clin Cancer Res. 2010;doi:10.1158/1078-0432.CCR-10-1507.
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Adoptive cell therapy administered with activated lymphocytes and interleukin-2 produced objective response in 50% of patients with metastatic brain melanoma in a study conducted by researchers at NIH.
From 2000 to 2009, patients were assigned to adoptive cell therapy consisting of cyclophosphamide and fludarabine with or without total-body irradiation and an infusion of autologous tumor infiltrating lymphocytes (TIL). Others were assigned to adoptive cell therapy with an infusion of autologous peripheral blood lymphocytes retrovirally transduced to express a T-cell receptor that recognized the melanocyte differentiation antigens gp100 or MART-1 (TCR).
Seventeen patients who underwent TIL with a lymphodepleting preparative regimen and bolus IL-2 had evaluable brain metastases. Seven (41%) had complete regression of all brain disease. Responses were ongoing at 4 to 44 months in five of those patients. Two of those who had complete regression in the brain also had partial response.
Median survival was 8.5 months with an estimated actuarial 2-year survival of approximately 40%.
Nine patients assigned to TCR gene-transduced lymphocytes with the same preparative regimen and IL-2 had evaluable brain metastases. One patient had complete regression lasting 8 months. Another had complete regression that was ongoing at 25 months. Median OS was 15 months, and researchers said no patient developed significant neurotoxicity as a result of the preparative regimen or lymphocyte infusion with IL-2.
Overall, 15 of 25 patients were still alive at the time of analysis and five of those had survived longer than 12 months without additional central nervous system therapy or systemic therapy.
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