Anti-CTLA-4 antibodies are human monoclonal antibodies previously studied in the treatment of metastatic melanoma (MM). CTLA-4 is an inhibitory receptor on cytotoxic T cells, blockade of which will activate T cells allowing them to attack malignant cells. Normal host cells may also be affected, and immune-mediated enterocolitis can occur. This is a prospective observational study on the use of corticosteroids and infliximab in the treatment of patients with immune-mediated colitis secondary to anti-CTLA-4 antibody treatment of MM. Five patients presented with colitis after medication administration. Patients were treated with high-dose corticosteroids for 1 week, but diarrhea did not completely abate in any of them. They were then treated successfully with infliximab. One patient had recurrence of symptoms and responded to repeat treatment with infliximab. Patients who develop immune-mediated colitis after administration of anti-CTLA-4 antibodies have previously been reported to respond to corticosteroids, but in our study, all required treatment with infliximab.
Colitis Antibodies Drug therapy Tremelimumab Infliximab T-Lymphocytes Immunology
This is a preview of subscription content, log in to check access.
Reuben JM, Lee BN, Li C, et al. Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in patients with advanced malignant melanoma. Cancer. 2006;106:2437–2444. doi:10.1002/cncr.21854.CrossRefPubMedGoogle Scholar
Pfizer announces discontinuation of phase III clinical trial for patients with advanced melanoma. Business Wire. 2008.Google Scholar
Medarex, Bristol-Myers delay BLA submission for ipilimumab; FDA seeks more data. Thomson Financial News. 2008.Google Scholar
Sanderson K, Scotland R, Lee P, et al. Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and montanide ISA 51 for patients with resected stages III and IV melanoma. J Clin Oncol. 2005;23:741–750. doi:10.1200/JCO.2005.01.128.CrossRefPubMedGoogle Scholar
Keler T, Halk E, Vitale L, et al. Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques. J Immunol. 2003;171:6251–6259.PubMedGoogle Scholar
Attia P, Phan GQ, Maker AV, et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anticytotoxic T-lymphocyte antigen-4. J Clin Oncol. 2005;23:6043–6053. doi:10.1200/JCO.2005.06.205.CrossRefPubMedGoogle Scholar