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CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS

Nature Clinical Practice Oncology volume 5, pages 557–561 (2008)Cite this article

Abstract

Background A 63-year-old female presented to her primary physician with numbness and weakness in her left leg, which progressed over several days to involve her entire lower extremities. MRI of the spine and brain revealed multiple metastases. The patient received ipilimumab and after 3 months experienced intermittent confusion and focal seizures.

Investigations Electroencephalogram and MRI scans of the spine and brain, followed by surgical removal of a left frontal cortical brain metastasis and subsequent histological and pathological analyses.

Diagnosis Metastatic melanoma from an unknown primary tumor.

Management The patient was treated with ipilimumab on a compassionate-use program and dexamethasone, celecoxib, and levetiracetam to treat the symptoms and seizures. Postoperative stereotactic radiosurgery was initiated.

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Figure 1: Radiographic changes to melanoma metastases in the brain with administration of CTLA-4 blockade.
Figure 2: MRI scans of the patient's spine 6 months after treatment with dexamethasone.
Figure 3: Pathological examination of resected brain metastasis following ipilimumab treatment.
Figure 4: Pathological assessment of immune effector cells associated with melanoma brain metastases following ipilimumab treatment.

References

  1. Aoyama H et al. (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295: 2483–2491

    Article  CAS  Google Scholar 

  2. Kerman AJ et al. (2006) Checkpoint blockade in cancer immunotherapy. Adv Immunol 90: 297–339

    Article  Google Scholar 

  3. Bafaloukos D and Gogas H (2004) The treatment of brain metastases in melanoma patients. Cancer Treat Rev 30: 515–520

    Article  CAS  Google Scholar 

  4. Barth A et al. (1995) Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg 181: 193–201

    CAS  PubMed  Google Scholar 

  5. Sampson JH et al. (1998) Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg 88: 11–20

    Article  CAS  Google Scholar 

  6. McDermott DF et al (2000) A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin 2, and interferon alpha-2B in patients with metastatic melanoma. Clin Cancer Res 6: 2201–2208

    CAS  PubMed  Google Scholar 

  7. Read S et al. (2006) Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo. J Immunol 177: 4376–4383

    Article  CAS  Google Scholar 

  8. Dunn GP et al. (2007) Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun 7: 12

    PubMed  PubMed Central  Google Scholar 

  9. Prins RM et al. (2006) The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: relation to central nervous system antitumor immunity. J Immunol 176: 157–164

    Article  CAS  Google Scholar 

  10. Liau LM et al. (2005) Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res 11: 5515–5525

    Article  CAS  Google Scholar 

  11. El Andaloussi A and Lesniak MS (2007) CD4+ CD25+ FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas. J Neurooncol 83: 145–152

    Article  CAS  Google Scholar 

  12. Grauer OM et al. (2007) CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int J Cancer 121: 95–105

    Article  CAS  Google Scholar 

  13. Carson MJ et al. (2006) CNS immune privilege: hiding in plain sight. Immunol Rev 213: 48–65

    Article  Google Scholar 

  14. O'Day S and Boasberg P (2006) Management of metastatic melanoma 2005. Surg Oncol Clin N Am 15: 419–437

    Article  Google Scholar 

  15. Attia P et al. (2005) Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 23: 6043–6053

    Article  CAS  Google Scholar 

  16. Hodi FS et al. (2003) Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA 100: 4712–4717

    Article  CAS  Google Scholar 

  17. Phan GQ et al. (2003) Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 100: 8372–8377

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Rebecca Turner for editorial assistance. Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. FS Hodi is Clinical Director of the Melanoma Program at the Dana–Farber Cancer Institute, Boston, MA,

    F Stephen Hodi

  2. DA Oble is a Hematopathology Fellow at the Columbia University Medical Center/New York Presbyterian Hospital, New York, NY,

    Darryl A Oble

  3. J Drappatz is a Neurologist at Brigham and Women's/Dana–Farber Cancer Center, Boston, MA, USA.,

    Jan Drappatz

  4. EF Velazquez is an Assistant Professor in the Department of Pathology at Harvard School of Medicine and an Associate Dermatopathologist at the Brigham and Women's Hospital, Boston, MA, USA.,

    Elsa F Velazquez

  5. N Ramaiya is Clinical Director MRI, at the Dana–Farber Cancer Institute, Boston, MA, USA.,

    Nikhil Ramaiya

  6. N Ramakrishna is Chief of the Division of CNS Radiation Oncology at Brigham and Women's Hospital and Dana–Farber Cancer Institute, Boston, MA, USA.,

    Naren Ramakrishna

  7. AL Day is Chief of the Department of Neurosurgery at the Brigham and Women's/Children's Hospitals, Boston, MA, USA.,

    Arthur L Day

  8. A Kruse is a Project Manager for melanoma clinical trials at the Dana–Farber Cancer Institute, Boston, MA, USA.,

    Andrea Kruse

  9. S MacRae is the Research Nurse for the Dana–Farber Cancer Institute Melanoma Program, Boston, MA, USA.,

    Suzanne Mac Rae

  10. A Hoos is Medical Lead in Immunology/Oncology at Bristol-Myers Squibb and is also President of the Cancer Vaccine Consortium and a Member of the Board of Trustees of the Albert B Sabin Vaccine Institute, Boston, MA, USA.,

    Axel Hoos

  11. M Mihm is Clinical Professor of Dermatology and Pathology at Harvard Medical School and Senior Dermatopathologist at the Massachusetts General Hospital, Boston, MA, USA.,

    Martin Mihm

Authors
  1. F Stephen Hodi
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  2. Darryl A Oble
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  3. Jan Drappatz
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  4. Elsa F Velazquez
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  5. Nikhil Ramaiya
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  6. Naren Ramakrishna
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  7. Arthur L Day
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  8. Andrea Kruse
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  10. Axel Hoos
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Corresponding author

Correspondence to F Stephen Hodi.

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Competing interests

FS Hodi is a Consultant and receives grant/research support from Bristol-Myers Squibb. A Hoos is an employee and stock-holder with Bristol-Myers Squibb. The other authors declared no competing interests.

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Hodi, F., Oble, D., Drappatz, J. et al. CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS. Nat Rev Clin Oncol 5, 557–561 (2008). https://doi.org/10.1038/ncponc1183

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