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. 2010 Oct 1;16(19):4892-8.
doi: 10.1158/1078-0432.CCR-10-1507. Epub 2010 Aug 18.

Successful treatment of melanoma brain metastases with adoptive cell therapy

Jenny J Hong  1 , Steven A Rosenberg, Mark E Dudley, James C Yang, Donald E White, John A Butman, Richard M Sherry
Affiliations

Successful treatment of melanoma brain metastases with adoptive cell therapy

Jenny J Hong et al. Clin Cancer Res. .

Abstract

Purpose: To determine the objective response rate and response duration of melanoma brain metastases to adoptive cell therapy (ACT) with autologous antitumor lymphocytes plus interleukin-2 following a lymphodepleting preparative regimen.

Methods: Between 2000 and 2009, 264 patients with metastatic melanoma received ACT, consisting of cyclophosphamide and fludarabine with or without total body irradiation, followed by the infusion of autologous tumor-infiltrating lymphocytes (TIL) or autologous peripheral blood lymphocytes retrovirally transduced to express a T-cell receptor (TCR) that recognized the melanocyte differentiation antigens gp-100 or MART-1. From this group, 26 patients were retrospectively identified to have had untreated brain metastases and extracranial disease before receiving ACT. The response rate and duration of melanoma brain metastases, as well as the overall response rate, response duration, and survival for these patients, are presented.

Results: Seventeen of these 26 patients received ACT with TIL. Seven of these patients (41%) achieved a complete response in the brain, and six patients achieved an overall partial response. In the nine patients that received TCR-transduced lymphocytes, two patients achieved a complete response in the brain (22%) and one of these two achieved an overall partial response. One patient developed a tumor-associated subarachnoid hemorrhage during the thrombocytopenic phase of therapy and had an uneventful metastatectomy.

Conclusion: ACT with a nonmyeloablative preparative regimen using either TIL- or TCR gene-transduced cells and interleukin-2 can mediate complete and durable regression of melanoma brain metastases. This strategy can be used safely in selected patients with metastatic melanoma to the brain.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Figures

Fig. 1.
Fig. 1.
Resolution of multiple brain lesions in two patients treated with CD8-enriched TIL and IL-2 after preparative lymphodepleting regimens of Cy/Flu (A and B) or Cy/Flu + 6-Gy TBI (C and D). A and C, pretreatment magnetic resonance imaging. B, 14 months after cell transfer. D, 6 months after cell transfer.
Fig. 2.
Fig. 2.
CR of a brain metastasis in two patients treated with anti–MART-1 TCR-transduced peripheral blood lymphocytes and IL-2 following a preparative regimen of Cy/Flu. A and C, pretreatment magnetic resonance imaging. B, 6 months after cell transfer. D, 30 months after cell transfer.
Fig. 3.
Fig. 3.
Kaplan-Meier estimates of overall survival for melanoma patients with untreated brain metastases before ACT.
See this image and copyright information in PMC

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