Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab

• Few treatments for metastatic melanoma provide long term tumor regressions.
• Response rate of 15.6% observed in 143 patients treated with tremelimumab.
• Patients with tumor response to tremelimumab very likely to have durable responses.
• Ten and 12.5 year estimated survival rates of 16% observed in these patients.
• Anti-CTLA-4 memory immune responses against tumors can last beyond a decade.

PurposeOne of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. Tremelimumab is an anti-CTLA-4 antibody of immunoglobulin G2 (IgG2) isotype initially tested in patients with advanced melanoma over 12 years ago.MethodsWe reviewed the outcomes of patients with advanced melanoma enrolled in four phase 1 and 2 tremelimumab trials at two sites to determine response rates and long-term survival.ResultsA total of 143 patients were enrolled at two institutions from 2002 to 2008. Tremelimumab administration varied between a single dose of 0.01 mg/kg and 15 mg/kg every 3 months. Median overall survival was 13 months (95% confidence interval (CI), 10–16.6), ranging from less than a month to 12+ years. An objective response rate of 15.6% was observed, with median duration of response of 6.5 years, range of 3–136+ months. The Kaplan–Meier estimated 5 year survival rate was 20% (95% CI, 13–26%), with 10 and 12.5 year survival rates of 16% (95% CI, 9–23%).ConclusionsCTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumour responses beyond 12 years.