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A systemic complete response of metastatic melanoma to local radiation and immunotherapy.

ABSTRACT: BACKGROUND:Melanoma is a relatively immunogenic tumor, in which infiltration of melanoma cells by T lymphocytes is associated with a better clinical prognosis. We hypothesized that radiation-induced cell death may provide additional stimulation of an anti-tumor immune response in the setting of anti-CTLA-4 treatment. METHODS:In a pilot melanoma patient, we prospectively tested this hypothesis. We treated the patient with two cycles of ipilimumab, followed by stereotactic ablative radiotherapy to two of seven hepatic metastases, and two additional cycles of ipilimumab. RESULTS:Subsequent positron emission tomography-computed tomography scan indicated that all metastases, including unirradiated liver lesions and an unirradiated axillary lesion, had completely resolved, consistent with a complete response by RECIST. CONCLUSION:The use of radiotherapy in combination with targeted immunotherapy as a noninvasive in vivo tumor vaccine strategy appears to be a promising method of enhancing the induction of systemic immune responses and anti-tumor effect.

SUBMITTER: Hiniker SM

PROVIDER: S-EPMC3542835 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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A systemic complete response of metastatic melanoma to local radiation and immunotherapy.

Hiniker Susan M SM Chen Daniel S DS Reddy Sunil S Chang Daniel T DT Jones Jennifer C JC Mollick Joseph A JA Swetter Susan M SM Knox Susan J SJ

Translational oncology 20121201 6

<h4>Background</h4>Melanoma is a relatively immunogenic tumor, in which infiltration of melanoma cells by T lymphocytes is associated with a better clinical prognosis. We hypothesized that radiation-induced cell death may provide additional stimulation of an anti-tumor immune response in the setting of anti-CTLA-4 treatment.<h4>Methods</h4>In a pilot melanoma patient, we prospectively tested this hypothesis. We treated the patient with two cycles of ipilimumab, followed by stereotactic ablative ...[more]

PMID: 23323154

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Project description:PurposeLocal radiation therapy (RT) combined with systemic anti-cytotoxic T-lymphocyte-associated protein-4 immunotherapy may enhance induction of systemic antimelanoma immune responses. The primary objective of the present trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. The secondary objectives included laboratory assessment of induction of antimelanoma immune responses.Methods and materialsIn our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1 to 2 disease sites was initiated within 5 days after starting ipilimumab. Patients had ≥1 nonirradiated metastasis measuring ≥1.5 cm available for response assessment. Tumor imaging studies were obtained at baseline, 2 to 4 weeks after cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment.ResultsCombination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) experienced clinical benefit from therapy, including complete and partial responses and stable disease at median follow-up of 55 weeks. Three patients (27.3%) achieved an ongoing systemic complete response at a median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had an initial partial response for a median of 40 weeks. Analysis of immune response data suggested a relationship between elevated CD8-activated T-cells and response.ConclusionThis is the second prospective clinical trial of treatment of metastatic melanoma using the combination of RT and systemic immunotherapy and the first using this sequence of therapy. The results from the present trial demonstrate that a subset of patients may benefit from combination therapy, arguing for continued clinical investigation of the use of RT combined with immunotherapy, including programmed cell death 1 inhibitors, which might have the potential to be even more effective in combination with RT.

Dataset Information

A systemic complete response of metastatic melanoma to local radiation and immunotherapy.

Publications

A systemic complete response of metastatic melanoma to local radiation and immunotherapy.

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