Immune response and stage 4 melanoma

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Stage 4 (Stage IV) melanoma is very difficult to treat.  Even though stage I melanoma has an excellent prognosis; response rate for stage 4 melanoma with palliative biotherapies and chemotherapies is only approximately 10%.

Clinicians and researchers are working hard to find treatment options for patients with stage 4 disease.  Despite treatment failure of radiotherapy and chemotherapy in melanoma, they repeatedly note anti-tumor immune responses with regression of metastases or disease stabilization.  These findings imply that melanoma is immune-related.

I found the article by Dr. Michael Erdmann in the February issue of The Lancet Oncology very interesting.  He discussed findings from recent trials on two anti-CTLA-4 agents, ipilimumab and tremelimumab.  They are both immunomodulating antibodies targeting CTLA-4.  While phase 2 study of ipilimumab has shown some clinical responses with best overall response rate of 11.1%, phase 3 study of tremelimumab was terminated due to lack of superiority compared to chemotherapy (dacarbazine or temozololomide).  Note that response rate of ipilimumab is comparable to chemotherapy.  However, it is important that prolonged disease stabilization in the selected subset of responsive patients is different.  The author explained activation of immune system by blocking CTLA-4 is a double-edged sword.  Ipilimumab has been associated with dose-dependent immune-related adverse events like enterocolitis and hypophysitis with irreversible disability.

Researchers’ next challenge is to prove ipilimumab’s superiority to chemo in phase 3 trials and hopefully they can identify biomarkers to identify or predict melanoma patients whom will respond to these CTLA-4 agents.

Erdmann MK, Immunity unleashed in melanoma; Lancet Oncol 2010, 11; 108-109

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