Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial

Introduction In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients w...

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Main Authors: John Haanen, Marco Donia, Inge Marie Svane, Bastiaan Nuijen, Cynthia Nijenhuis, Valesca P Retèl, Tine Monberg, Renske M T ten Ham, Maartje W Rohaan, Inge Jedema, Rob Kessels, Wim Stegeman, Walter Scheepmaker, Melanie Lindenberg, Wim van Harten
Format: Article
Language:English
Published: BMJ Publishing Group 2024-03-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/3/e008372.full
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author John Haanen
Marco Donia
Inge Marie Svane
Bastiaan Nuijen
Cynthia Nijenhuis
Valesca P Retèl
Tine Monberg
Renske M T ten Ham
Maartje W Rohaan
Inge Jedema
Rob Kessels
Wim Stegeman
Walter Scheepmaker
Melanie Lindenberg
Wim van Harten
author_facet John Haanen
Marco Donia
Inge Marie Svane
Bastiaan Nuijen
Cynthia Nijenhuis
Valesca P Retèl
Tine Monberg
Renske M T ten Ham
Maartje W Rohaan
Inge Jedema
Rob Kessels
Wim Stegeman
Walter Scheepmaker
Melanie Lindenberg
Wim van Harten
author_sort John Haanen
collection DOAJ
description Introduction In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC–IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis.Methods A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands. The Danish setting was assessed in a scenario analysis. A modified societal perspective was applied over a lifetime horizon. TIL-NKI/CCIT production costs were estimated via activity-based costing. Through sensitivity analyses, uncertainties and their impact on the incremental cost-effectiveness ratio (ICER) were assessed.Results Mean total undiscounted lifetime benefits were 4.47 life years (LYs) and 3.52 QALYs for TIL-NKI/CCIT and 3.33 LYs and 2.46 QALYs for ipilimumab. Total lifetime undiscounted costs in the Netherlands were €347,168 for TIL-NKI/CCIT (including €67,547 for production costs) compared with €433,634 for ipilimumab. Undiscounted lifetime cost in the Danish scenario were €337,309 and €436,135, respectively. This resulted in a dominant situation for TIL-NKI/CCIT compared with ipilimumab in both countries, meaning incremental QALYs were gained at lower costs. Survival probabilities, and utility in progressive disease affected the ICER most.Conclusion Based on the data of a randomized phase 3 trial, treatment with TIL-NKI/CCIT in patients with unresectable stage IIIC–IV melanoma is cost-effective and cost-saving, both in the current Dutch and Danish setting. These findings led to inclusion of TIL-NKI/CCIT as insured care and treatment guidelines. Publicly funded development of the TIL-NKI/CCIT cell therapy shows realistic promise to further explore development of effective personalized treatment while warranting economic sustainability of healthcare systems.
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spelling doaj-art-861ff4b06089417c8f45e19942083ea22024-12-18T03:45:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-03-0112310.1136/jitc-2023-008372Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trialJohn Haanen0Marco DoniaInge Marie Svane1Bastiaan Nuijen2Cynthia Nijenhuis3Valesca P Retèl4Tine Monberg5Renske M T ten Ham6Maartje W Rohaan7Inge Jedema8Rob Kessels9Wim Stegeman10Walter Scheepmaker11Melanie Lindenberg12Wim van Harten13Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, The NetherlandsNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, DenmarkDepartment of Pharmacy and Pharmacology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, The Netherlands8 Biotherapeutics Unit, Netherlands Cancer Institute, Amsterdam, The Netherlands12 Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands9 Department of Oncology, National Center for Cancer Immune Therapy, Copenhagen University Hospital, Herlev, Denmark1 Department of Epidemiology & Health Economics, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands3 Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands4 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands5 Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands5 Department of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands6 Financial Department, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The NetherlandsIntroduction In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC–IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis.Methods A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands. The Danish setting was assessed in a scenario analysis. A modified societal perspective was applied over a lifetime horizon. TIL-NKI/CCIT production costs were estimated via activity-based costing. Through sensitivity analyses, uncertainties and their impact on the incremental cost-effectiveness ratio (ICER) were assessed.Results Mean total undiscounted lifetime benefits were 4.47 life years (LYs) and 3.52 QALYs for TIL-NKI/CCIT and 3.33 LYs and 2.46 QALYs for ipilimumab. Total lifetime undiscounted costs in the Netherlands were €347,168 for TIL-NKI/CCIT (including €67,547 for production costs) compared with €433,634 for ipilimumab. Undiscounted lifetime cost in the Danish scenario were €337,309 and €436,135, respectively. This resulted in a dominant situation for TIL-NKI/CCIT compared with ipilimumab in both countries, meaning incremental QALYs were gained at lower costs. Survival probabilities, and utility in progressive disease affected the ICER most.Conclusion Based on the data of a randomized phase 3 trial, treatment with TIL-NKI/CCIT in patients with unresectable stage IIIC–IV melanoma is cost-effective and cost-saving, both in the current Dutch and Danish setting. These findings led to inclusion of TIL-NKI/CCIT as insured care and treatment guidelines. Publicly funded development of the TIL-NKI/CCIT cell therapy shows realistic promise to further explore development of effective personalized treatment while warranting economic sustainability of healthcare systems.https://jitc.bmj.com/content/12/3/e008372.full
spellingShingle John Haanen
Marco Donia
Inge Marie Svane
Bastiaan Nuijen
Cynthia Nijenhuis
Valesca P Retèl
Tine Monberg
Renske M T ten Ham
Maartje W Rohaan
Inge Jedema
Rob Kessels
Wim Stegeman
Walter Scheepmaker
Melanie Lindenberg
Wim van Harten
Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial
Journal for ImmunoTherapy of Cancer
title Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial
title_full Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial
title_fullStr Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial
title_full_unstemmed Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial
title_short Cost-effectiveness of treating advanced melanoma with tumor-infiltrating lymphocytes based on an international randomized phase 3 clinical trial
title_sort cost effectiveness of treating advanced melanoma with tumor infiltrating lymphocytes based on an international randomized phase 3 clinical trial
url https://jitc.bmj.com/content/12/3/e008372.full
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