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. 2015 Nov;51(17):2689-97.
doi: 10.1016/j.ejca.2015.08.012. Epub 2015 Sep 10.

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

Zeynep Eroglu  1 , Dae Won Kim  2 , Xiaoyan Wang  3 , Luis H Camacho  4 , Bartosz Chmielowski  5 , Elizabeth Seja  5 , Arturo Villanueva  5 , Kathleen Ruchalski  6 , John A Glaspy  5 , Kevin B Kim  7 , Wen-Jen Hwu  2 , Antoni Ribas  8
Affiliations

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

Zeynep Eroglu et al. Eur J Cancer. 2015 Nov.

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.

Keywords: Anti-CTLA-4 therapy; Immunotherapy; Melanoma; Tremelimumab.

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Figures

Figure 1
Figure 1
Swimmer Plot. Each bar represents one subject. Blue bars indicate the time to and duration of response while on treatment; yellow bars indicate response duration after treatment discontinuation. Triangles indicate start of best response; circles indicate end of best response. Right arrows indicate ongoing response at time of last follow-up.
Figure 2
Figure 2
Two patients with long lasting complete responses with tremelimumab therapy. A) Patient A367-1001-125 - Baseline study from 1.7.2003 with arrows depicting peritoneal carcinomatosis. B) Maintained complete response in 12.26.2012 in the same regions of previously visualized omental thickening and nodularity C) Patient NRA9: Arrow pointing to right lower lobe pulmonary nodule on 11.28.2005 D) Right lower lobe nodule is no longer visualized on PET-CT 8.13.2013
Figure 3
Figure 3
Overall survival for all patients
See this image and copyright information in PMC

Comment in

  • How should we use anti-CTLA-4 antibodies?
    Marabelle A, Eggermont A. Marabelle A, et al. Eur J Cancer. 2015 Nov;51(17):2686-8. doi: 10.1016/j.ejca.2015.09.002. Eur J Cancer. 2015. PMID: 26613660 No abstract available.

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