Zeynep Eroglu1, Dae Won Kim2, Xiaoyan Wang3, Luis H Camacho4, Bartosz Chmielowski5, Elizabeth Seja5, Arturo Villanueva5, Kathleen Ruchalski6, John A Glaspy5, Kevin B Kim7, Wen-Jen Hwu2, Antoni Ribas8. 1. Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA. 2. Department of Melanoma Medical Oncology, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA. 3. Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA, USA. 4. St. Luke's Medical Center Cancer Center, Houston, TX, USA. 5. Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA. 6. Department of Radiology, University of California Los Angeles, Los Angeles, CA, USA. 7. Department of Melanoma Medical Oncology, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA; California Pacific Medical Center, San Francisco, CA, USA. 8. Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu.
Abstract
PURPOSE: One 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. METHODS: We 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. RESULTS: A 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%). CONCLUSIONS: CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumour responses beyond 12 years.
PURPOSE: One 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. METHODS: We 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. RESULTS: A 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%). CONCLUSIONS:CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumour responses beyond 12 years.
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