Evaluating different adoption scenarios for TIL-therapy and the influence on its (early) cost-effectiveness

Abstract

Background: Treatment with tumor-Infiltrating Lymphocytes (TIL) is an innovative therapy for advanced melanoma with promising clinical phase I/II study results and likely beneficial cost-effectiveness. As a randomized controlled trial on the effectiveness of TIL therapy in advanced melanoma compared to ipilimumab is still ongoing, adoption of TIL therapy by the field is confronted with uncertainty. To deal with this, scenario drafting can be used to identify potential barriers and enables the subsequent anticipation on these barriers. This study aims to inform adoption decisions of TIL by evaluating various scenarios and evaluate their effect on the cost-effectiveness. Methods: First, 14 adoption scenarios for TIL-therapy were drafted using a Delphi approach with a group of involved experts. Second, the likelihood of the scenarios taking place within 5 years was surveyed among international experts using a web-based questionnaire. Third, based on the questionnaire results and recent literature, scenarios were labeled as being either "likely" or "-unlikely". Finally, the cost-effectiveness of TIL treatment involving the "likely" scored scenarios was calculated. Results: Twenty-nine experts from 12 countries completed the questionnaire. The scenarios showed an average likelihood ranging from 29 to 58%, indicating that future developments of TIL-therapy were surrounded with quite some uncertainty. Eight of the 14 scenarios were labeled as "likely". The net monetary benefit per patient is presented as a measure of cost-effectiveness, where a positive value means that a scenario is cost-effective. For six of these scenarios the cost-effectiveness was calculated: "Commercialization of TIL production" (the price was assumed to be 3 times the manufacturing costs in the academic setting) (−€51,550), "Pharmaceutical companies lowering the prices of ipilimumab" (€11,420), "Using TIL-therapy combined with ipilimumab" (−€10,840), "Automatic TIL production" (€22,670), "TIL more effective" (€23,270), "Less Interleukin-2" (€20,370).

Cost‐effectiveness of a policy‐based intervention to reduce melanoma and other skin cancers associated with indoor tanning*

“…The key limitation of this study was our reliance on publicly available data that may not reflect current clinical and tanning practices. While robust estimates for model input values could be identified in the published literature, this was not true for costs and clinical effectiveness of current diagnosis, treatment and monitoring options for patients with melanoma 35 . Advanced melanoma treatments have increased dramatically in the last 10 years and adjuvant treatment of stage 3 melanoma has been approved, which suggests that our base‐case values are underestimated.…”

“…While robust estimates for model input values could be identified in the published literature, this was not true for costs and clinical effectiveness of current diagnosis, treatment and monitoring options for patients with melanoma. 35 Advanced melanoma treatments have increased dramatically in the last 10 years and adjuvant treatment of stage 3 melanoma has been approved, which suggests that our base-case values are underestimated. Clinical trials are under way in patients with stage 2 disease, a much larger patient population than stages 3 or 4.…”

Adoptive T Cell Therapy for Solid Tumors: Pathway to Personalized Standard of Care

“…The ex vivo TIL expansion protocol is labor-intensive and the requirement to use fresh TIL products for infusion impose further restrictions on the implantation. Outsourcing TIL production to dedicated manufacturing centers is necessary to increase the cost-effectiveness and expand the availability of this therapy [ 124 ]. Iovance Biotherapeutics has established a centralized, high-throughput manufacturing facility for the production of cryopreserved TILs (brand named Lifleucel).…”

“…Despite the fact that TIL-ACT has yet to be FDA approved for the treatment of solid malignancies, strong preclinical and clinical results support its potential in eliciting durable tumor regression. therapy [124]. Iovance Biotherapeutics has established a centralized, high-throughput manufacturing facility for the production of cryopreserved TILs (brand named Lifleucel).…”

Synthetic TILs: Engineered Tumor-Infiltrating Lymphocytes With Improved Therapeutic Potential

“…TIL-based ACT in combination with high-dose IL-2 have been shown to be an effective clinical strategy in MM patients, and to a lesser extent, in other tumors. Although many issues remain to be addressed, especially regarding the relatively long generation process and the requirement for GMP facilities and trained personnel, the early-treatment costs are considerably lower than those of anti-CTLA4 mAb in MM ( 85 ). Given than TILs are naturally infiltrating cells, they can also serve as biomarker to predict the clinical efficacy of immunotherapies enhancing antitumor adaptive responses ( 86 ) Interestingly, different approaches have recently demonstrated that during the ex vivo process necessary for TIL generation, these tumor-specific T cells can be efficiently genetically modified in order to enhance their cytotoxicity, tumor homing or to reduce T cell exhaustion.…”