Development of brain metastases in patients with metastatic melanoma while receiving ipilimumab.
Ipilimumab is a monoclonal antibody blocking the inhibitory molecule CTLA4 expressed by activated T lympocytes, used for the treatment of metastatic melanoma. Recent studies have shown its potential efficacy on brain metastases.


OBJECTIVE
To assess the development of brain metastases under ipilimumab and identify clinical, histological or evolving criteria related to the appearance of these metastases. A retrospective study was conducted in 52 patients treated with 4 cycles of ipilimumab 3 mg/kg every 3 weeks for unresectable stage III or stage IV melanoma between January 2011 and July 2013 in a Department of Dermato-Oncology. As no data has been find in the literature, the results were compared to our other cohort of patients treated with vemurafenib during the same period. Ten patients (21.7 %) developed brain metastases under ipilimumab in a median time of 6.58 months after treatment initiation. The multivariate analysis showed a lower rate of brain metastases in patients with acral lentiginous melanoma and melanoma of unknown primary site. The median survival after diagnosis of brain metastases was of 2.5 months. There was no significant difference with vemurafenib-treated patients in terms of incidence rate of brain metastasis, time of development and survival after diagnosis of cerebral metastases. This was the first study focused on the development of brain metastases under treatment with ipilimumab 3 mg/kg. Although ipilimumab is used for the treatment of brain metastases, it paradoxically did not seem to reduce the risk of developing brain metastases.
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
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Frenard
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
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Peuvrel
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
M Saint
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Jean
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
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Brocard
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
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Knol
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
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JM
Nguyen
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
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A
Khammari
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France.
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Quereux
Department of dermatology, Skin Cancer Unit, Nantes University Hospital, INSERM 892, 1 place Alexis Ricordeau, 44093, Nantes Cedex 1, France. brigitte.dreno@wanadoo.fr.
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B
Dreno
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000074324:Ipilimumab
Brain metastases; Ipilimumab; Melanoma