Skip to main content
Top
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Early cost-effectiveness of tumor infiltrating lymphocytes (TIL) for second line treatment in advanced melanoma: a model-based economic evaluation

Authors: Valesca P. Retèl, Lotte M. G. Steuten, Marnix H. Geukes Foppen, Janne C. Mewes, Melanie A. Lindenberg, John B. A. G. Haanen, Wim H. van Harten

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

An emerging immunotherapy is infusion of tumor infiltrating Lymphocytes (TIL), with objective response rates of around 50% versus 19% for ipilimumab. As an Advanced Therapeutic Medicinal Products (ATMP), TIL is highly personalized and complex therapy. It requests substantial upfront investments from the hospital in: expensive lab-equipment, staff expertise and training, as well as extremely tight hospital logistics. Therefore, an early health economic modelling study, as part of a Coverage with Evidence Development (CED) program, was performed.

Methods

We used a Markov decision model to estimate the expected costs and outcomes (quality-adjusted life years; QALYs) for TIL versus ipilimumab for second line treatment in metastatic melanoma patients from a Dutch health care perspective over a life long time horizon. Three mutually exclusive health states (stable disease (responders)), progressive disease and death) were modelled. To inform further research prioritization, Value of Information (VOI) analysis was performed.

Results

TIL is expected to generate more QALYs compared to ipilimumab (0.45 versus 0.38 respectively) at lower incremental cost (presently €81,140 versus €94,705 respectively) resulting in a dominant ICER (less costly and more effective). Based on current information TIL is dominating ipilimumab and has a probability of 86% for being cost effective at a cost/QALY threshold of €80,000. The Expected Value of Perfect Information (EVPI) amounted to €3 M.

Conclusions

TIL is expected to have the highest probability of being cost-effective in second line treatment for advanced melanoma compared to ipilimumab. To reduce decision uncertainty, a clinical trial investigating e.g. costs and survival seems most valuable. This is currently being undertaken as part of a CED program in the Netherlands Cancer Institute, Amsterdam, the Netherlands, in collaboration with Denmark.
Literature
1.
go back to reference Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007;109:455–64.CrossRef Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007;109:455–64.CrossRef
2.
go back to reference Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.CrossRef Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.CrossRef
3.
go back to reference Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:1270–1.CrossRef Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:1270–1.CrossRef
4.
go back to reference Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372:2521–32.CrossRef Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372:2521–32.CrossRef
5.
go back to reference Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008;8:299–308.CrossRef Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008;8:299–308.CrossRef
6.
go back to reference Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.CrossRef Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.CrossRef
7.
go back to reference Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17:4550–7.CrossRef Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17:4550–7.CrossRef
8.
go back to reference Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, et al. Long-lasting complete responses in patients with metastatic melanoma after adoptive cell therapy with tumor-infiltrating lymphocytes and an attenuated IL2 regimen. Clin Cancer Res. 2016;22:3734–45.CrossRef Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, et al. Long-lasting complete responses in patients with metastatic melanoma after adoptive cell therapy with tumor-infiltrating lymphocytes and an attenuated IL2 regimen. Clin Cancer Res. 2016;22:3734–45.CrossRef
9.
go back to reference Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26:5233–9.CrossRef Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26:5233–9.CrossRef
10.
go back to reference Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, et al. Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2010;16:2646–55.CrossRef Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, et al. Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2010;16:2646–55.CrossRef
11.
go back to reference Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2012;18:6758–70.CrossRef Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2012;18:6758–70.CrossRef
12.
go back to reference Svane IM, Verdegaal EM. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care? Cancer Immunol Immunother. 2014;63:1081–91.CrossRef Svane IM, Verdegaal EM. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma: what is needed to achieve standard of care? Cancer Immunol Immunother. 2014;63:1081–91.CrossRef
13.
go back to reference Hutton J, Trueman P, Henshall C. Coverage with evidence development: an examination of conceptual and policy issues. Int J Technol Assess Health Care. 2007;23:425–32.CrossRef Hutton J, Trueman P, Henshall C. Coverage with evidence development: an examination of conceptual and policy issues. Int J Technol Assess Health Care. 2007;23:425–32.CrossRef
14.
go back to reference Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst. 2000;92:205–16.PubMed Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada J Natl Cancer Inst. 2000;92:205–16.PubMed
15.
go back to reference Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated health economic evaluation reporting standards (CHEERS)--explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force. Value Health. 2013;16:231–50.CrossRef Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated health economic evaluation reporting standards (CHEERS)--explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force. Value Health. 2013;16:231–50.CrossRef
16.
go back to reference National Institute for Health and Care Excellence (NICE). Ipilimumab for previously treated advanced (unresectable or metastatic) melanoma (TA268). In; 2012. National Institute for Health and Care Excellence (NICE). Ipilimumab for previously treated advanced (unresectable or metastatic) melanoma (TA268). In; 2012.
17.
go back to reference Biostat. CMA Software. In. version 3 ed. USA. Biostat. CMA Software. In. version 3 ed. USA.
18.
go back to reference Beusterien KM, Szabo SM, Kotapati S, Mukherjee J, Hoos A, Hersey P, et al. Societal preference values for advanced melanoma health states in the United Kingdom and Australia. Br J Cancer. 2009;101:387–9.CrossRef Beusterien KM, Szabo SM, Kotapati S, Mukherjee J, Hoos A, Hersey P, et al. Societal preference values for advanced melanoma health states in the United Kingdom and Australia. Br J Cancer. 2009;101:387–9.CrossRef
20.
go back to reference Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, et al. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin Cancer Res. 2013;19:4792–800.CrossRef Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, et al. Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies. Clin Cancer Res. 2013;19:4792–800.CrossRef
21.
go back to reference Geukes Foppen MH, Donia M, Svane IM, Haanen JB. Tumor-infiltrating lymphocytes for the treatment of metastatic cancer. Mol Oncol. 2015;9:1918–35.CrossRef Geukes Foppen MH, Donia M, Svane IM, Haanen JB. Tumor-infiltrating lymphocytes for the treatment of metastatic cancer. Mol Oncol. 2015;9:1918–35.CrossRef
23.
go back to reference Barzey V, Atkins MB, Garrison LP, Asukai Y, Kotapati S, Penrod JR. Ipilimumab in 2nd line treatment of patients with advanced melanoma: a cost-effectiveness analysis. J Med Econ. 2013;16:202–12.CrossRef Barzey V, Atkins MB, Garrison LP, Asukai Y, Kotapati S, Penrod JR. Ipilimumab in 2nd line treatment of patients with advanced melanoma: a cost-effectiveness analysis. J Med Econ. 2013;16:202–12.CrossRef
24.
go back to reference Ellebaek E, Iversen TZ, Junker N, Donia M, Engell-Noerregaard L, Met O, et al. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. J Transl Med. 2012;10:169.CrossRef Ellebaek E, Iversen TZ, Junker N, Donia M, Engell-Noerregaard L, Met O, et al. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. J Transl Med. 2012;10:169.CrossRef
25.
go back to reference Hakkaart-van Roijen L vdLN, Bouwmans C, Kanters T, Tan SS,. Kostenhandleiding. Methodologie van kostenonderzoek en referentieprijzen voor economische evaluaties in de gezondheidszorg. (in Dutch). In opdracht van Zorginstituut Nederland. 2015. Hakkaart-van Roijen L vdLN, Bouwmans C, Kanters T, Tan SS,. Kostenhandleiding. Methodologie van kostenonderzoek en referentieprijzen voor economische evaluaties in de gezondheidszorg. (in Dutch). In opdracht van Zorginstituut Nederland. 2015.
26.
go back to reference Weinstein MC. Recent developments in decision-analytic modelling for economic evaluation. PharmacoEconomics. 2006;24:1043–53.CrossRef Weinstein MC. Recent developments in decision-analytic modelling for economic evaluation. PharmacoEconomics. 2006;24:1043–53.CrossRef
27.
go back to reference Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ. 2001;10:779–87.CrossRef Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ. 2001;10:779–87.CrossRef
28.
go back to reference Vallejo-Torres L, Steuten LM, Buxton MJ, Girling AJ, Lilford RJ, Young T. Integrating health economics modeling in the product development cycle of medical devices: a Bayesian approach. Int J Technol Assess Health Care. 2008;24:459–64.CrossRef Vallejo-Torres L, Steuten LM, Buxton MJ, Girling AJ, Lilford RJ, Young T. Integrating health economics modeling in the product development cycle of medical devices: a Bayesian approach. Int J Technol Assess Health Care. 2008;24:459–64.CrossRef
29.
go back to reference Willan AR, Pinto EM. The value of information and optimal clinical trial design. Stat Med. 2005;24:1791–806.CrossRef Willan AR, Pinto EM. The value of information and optimal clinical trial design. Stat Med. 2005;24:1791–806.CrossRef
30.
go back to reference van Harten WH, Wind A, de Paoli P, Saghatchian M, Oberst S. Actual costs of cancer drugs in 15 European countries. Lancet Oncol. 2016;17:18–20.CrossRef van Harten WH, Wind A, de Paoli P, Saghatchian M, Oberst S. Actual costs of cancer drugs in 15 European countries. Lancet Oncol. 2016;17:18–20.CrossRef
Metadata
Title
Early cost-effectiveness of tumor infiltrating lymphocytes (TIL) for second line treatment in advanced melanoma: a model-based economic evaluation
Authors
Valesca P. Retèl
Lotte M. G. Steuten
Marnix H. Geukes Foppen
Janne C. Mewes
Melanie A. Lindenberg
John B. A. G. Haanen
Wim H. van Harten
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4788-5

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine