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Published in: Journal of Neuro-Oncology 2/2016

01-01-2016 | Clinical Study

Development of brain metastases in patients with metastatic melanoma while receiving ipilimumab

Authors: C. Frenard, L. Peuvrel, M. Saint Jean, A. Brocard, A. C. Knol, J. M. Nguyen, A. Khammari, G. Quereux, B. Dreno

Published in: Journal of Neuro-Oncology | Issue 2/2016

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Abstract

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. Objectives: 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.
Literature
1.
go back to reference Erdmann F, Lortet-Tieulent J, Schüz J, Zeeb H, Greinert R, Breitbart EW, Bray F (2013) International trends in the incidence of malignant melanoma 1953–2008—are recent generations at higher or lower risk? Int J Cancer 132:385–400PubMedCrossRef Erdmann F, Lortet-Tieulent J, Schüz J, Zeeb H, Greinert R, Breitbart EW, Bray F (2013) International trends in the incidence of malignant melanoma 1953–2008—are recent generations at higher or lower risk? Int J Cancer 132:385–400PubMedCrossRef
3.
go back to reference Davies MA, Liu P, McIntyre S, Kim KB, Papadopoulos N, Hwu W-J, Hwu P, Bedikian A (2011) Prognostic factors for survival in melanoma patients with brain metastases. Cancer 117:1687–1696PubMedCrossRef Davies MA, Liu P, McIntyre S, Kim KB, Papadopoulos N, Hwu W-J, Hwu P, Bedikian A (2011) Prognostic factors for survival in melanoma patients with brain metastases. Cancer 117:1687–1696PubMedCrossRef
4.
go back to reference Patel JK, Didolkar MS, Pickren JW, Moore RH (1978) Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg 135:807–810PubMedCrossRef Patel JK, Didolkar MS, Pickren JW, Moore RH (1978) Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg 135:807–810PubMedCrossRef
5.
go back to reference Hofmann M, Kiecker F, Wurm R, Schlenger L, Budach V, Sterry W, Trefzer U (2006) Temozolomide with or without radiotherapy in melanoma with unresectable brain metastases. J Neurooncol 76:59–64PubMedCrossRef Hofmann M, Kiecker F, Wurm R, Schlenger L, Budach V, Sterry W, Trefzer U (2006) Temozolomide with or without radiotherapy in melanoma with unresectable brain metastases. J Neurooncol 76:59–64PubMedCrossRef
6.
go back to reference Kim G, McKee AE, Ning Y-M et al (2014) FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAF V600E mutation. Clin Cancer Res Off J Am Assoc Cancer Res. doi:10.1158/1078-0432.CCR-14-0776 Kim G, McKee AE, Ning Y-M et al (2014) FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAF V600E mutation. Clin Cancer Res Off J Am Assoc Cancer Res. doi:10.​1158/​1078-0432.​CCR-14-0776
7.
go back to reference Graziani G, Tentori L, Navarra P (2012) Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharmacol Res 65:9–22PubMedCrossRef Graziani G, Tentori L, Navarra P (2012) Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharmacol Res 65:9–22PubMedCrossRef
8.
10.
go back to reference Di Giacomo AM, Ascierto PA, Pilla L et al (2012) Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol 13:879–886PubMedCrossRef Di Giacomo AM, Ascierto PA, Pilla L et al (2012) Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol 13:879–886PubMedCrossRef
11.
go back to reference Knisely JPS, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VLS (2012) Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg 117:227–233PubMedCrossRef Knisely JPS, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VLS (2012) Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg 117:227–233PubMedCrossRef
12.
13.
go back to reference Prins RM, Vo DD, Khan-Farooqi H, Yang M-Y, Soto H, Economou JS, Liau LM, Ribas A (2006) NK and CD4 cells collaborate to protect against melanoma tumor formation in the brain. J Immunol 177:8448–8455PubMedCrossRef Prins RM, Vo DD, Khan-Farooqi H, Yang M-Y, Soto H, Economou JS, Liau LM, Ribas A (2006) NK and CD4 cells collaborate to protect against melanoma tumor formation in the brain. J Immunol 177:8448–8455PubMedCrossRef
14.
go back to reference Takeshima T, Chamoto K, Wakita D, Ohkuri T, Togashi Y, Shirato H, Kitamura H, Nishimura T (2010) Local radiation therapy inhibits tumor growth through the generation of tumor-specific CTL: its potentiation by combination with Th1 cell therapy. Cancer Res 70:2697–2706PubMedCrossRef Takeshima T, Chamoto K, Wakita D, Ohkuri T, Togashi Y, Shirato H, Kitamura H, Nishimura T (2010) Local radiation therapy inhibits tumor growth through the generation of tumor-specific CTL: its potentiation by combination with Th1 cell therapy. Cancer Res 70:2697–2706PubMedCrossRef
15.
16.
go back to reference Cao Y, Tsien CI, Shen Z, Tatro DS, Ten Haken R, Kessler ML, Chenevert TL, Lawrence TS (2005) Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy. J Clin Oncol Off J Am Soc Clin Oncol 23:4127–4136CrossRef Cao Y, Tsien CI, Shen Z, Tatro DS, Ten Haken R, Kessler ML, Chenevert TL, Lawrence TS (2005) Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy. J Clin Oncol Off J Am Soc Clin Oncol 23:4127–4136CrossRef
17.
go back to reference Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE (2004) Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the metropolitan Detroit cancer surveillance system. J Clin Oncol 22:2865–2872PubMedCrossRef Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE (2004) Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the metropolitan Detroit cancer surveillance system. J Clin Oncol 22:2865–2872PubMedCrossRef
18.
go back to reference Schouten LJ, Rutten J, Huveneers HAM, Twijnstra A (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698–2705PubMedCrossRef Schouten LJ, Rutten J, Huveneers HAM, Twijnstra A (2002) Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer 94:2698–2705PubMedCrossRef
19.
go back to reference Amer MH, Al-Sarraf M, Baker LH, Vaitkevicius VK (1978) Malignant melanoma and central nervous system metastases. Incidence, diagnosis, treatment and survival. Cancer 42:660–668PubMedCrossRef Amer MH, Al-Sarraf M, Baker LH, Vaitkevicius VK (1978) Malignant melanoma and central nervous system metastases. Incidence, diagnosis, treatment and survival. Cancer 42:660–668PubMedCrossRef
20.
go back to reference Sampson JH, Carter JH Jr, Friedman AH, Seigler HF (1998) Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 88:11–20PubMedCrossRef Sampson JH, Carter JH Jr, Friedman AH, Seigler HF (1998) Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 88:11–20PubMedCrossRef
21.
go back to reference Raizer JJ, Hwu W-J, Panageas KS et al (2008) Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro-Oncol 10:199–207PubMedPubMedCentralCrossRef Raizer JJ, Hwu W-J, Panageas KS et al (2008) Brain and leptomeningeal metastases from cutaneous melanoma: survival outcomes based on clinical features. Neuro-Oncol 10:199–207PubMedPubMedCentralCrossRef
22.
go back to reference Bedikian AY, Wei C, Detry M, Kim KB, Papadopoulos NE, Hwu W-J, Homsi J, Davies M, McIntyre S, Hwu P (2011) Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma. Am J Clin Oncol 34:603–610PubMedCrossRef Bedikian AY, Wei C, Detry M, Kim KB, Papadopoulos NE, Hwu W-J, Homsi J, Davies M, McIntyre S, Hwu P (2011) Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma. Am J Clin Oncol 34:603–610PubMedCrossRef
23.
go back to reference Schoenewolf NL, Belloni B, Simcock M, Tonolla S, Vogt P, Scherrer E, Holzmann D, Dummer R (2014) Clinical implications of distinct metastasizing preferences of different melanoma subtypes. Eur J Dermatol EJD. doi:10.1684/ejd.2014.2292 PubMed Schoenewolf NL, Belloni B, Simcock M, Tonolla S, Vogt P, Scherrer E, Holzmann D, Dummer R (2014) Clinical implications of distinct metastasizing preferences of different melanoma subtypes. Eur J Dermatol EJD. doi:10.​1684/​ejd.​2014.​2292 PubMed
24.
go back to reference Gumusay O, Coskun U, Akman T et al (2014) Predictive factors for the development of brain metastases in patients with malignant melanoma: a study by the Anatolian society of medical oncology. J Cancer Res Clin Oncol 140:151–157PubMedCrossRef Gumusay O, Coskun U, Akman T et al (2014) Predictive factors for the development of brain metastases in patients with malignant melanoma: a study by the Anatolian society of medical oncology. J Cancer Res Clin Oncol 140:151–157PubMedCrossRef
25.
go back to reference Papadatos-Pastos D, Soultati A, Harries M (2013) Targeting brain metastases in patients with melanoma. BioMed Res Int 2013:1–6CrossRef Papadatos-Pastos D, Soultati A, Harries M (2013) Targeting brain metastases in patients with melanoma. BioMed Res Int 2013:1–6CrossRef
26.
go back to reference Posner JB, Chernik NL (1978) Intracranial metastases from systemic cancer. Adv Neurol 19:579–592PubMed Posner JB, Chernik NL (1978) Intracranial metastases from systemic cancer. Adv Neurol 19:579–592PubMed
Metadata
Title
Development of brain metastases in patients with metastatic melanoma while receiving ipilimumab
Authors
C. Frenard
L. Peuvrel
M. Saint Jean
A. Brocard
A. C. Knol
J. M. Nguyen
A. Khammari
G. Quereux
B. Dreno
Publication date
01-01-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1977-9

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