OP310 Challenges Raised By The Economic Evaluation Of CAR-T-cell therapies: The Review By The French National Authority For Health

2021 ◽  
Vol 37 (S1) ◽  
pp. 11-12
Author(s):  
Véronique Raimond ◽  
Emmanuelle Kaltenbach ◽  
Christophe Adam ◽  
Sébastien Lazzarotto ◽  
Catherine Le Galès ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Cost Effectiveness ◽  
T Cell ◽  
Budget Impact ◽  
Indirect Comparison ◽  
National Authority ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T

IntroductionSince 2013, the coverage of innovative and expensive drugs by the French National Health Insurance considers cost-effectiveness and budget impact, as assessed by the National Authority for Health (HAS) on the basis of an evaluation submitted by the firm. First CAR-T cell therapies were subject to economic evaluation in 2019 in France. We aim at describing the process and results of the economic evaluation of tisagenlecleucel and axicabtagene ciloleucel and the challenges these evaluations raised.MethodsPrimary evaluations were submitted by the firms to be reviewed by HAS. The final analyses were submitted to the Committee of Economic Evaluation and Public Health (CEESP), composed of independent economists, clinicians and patients’ representatives. The CEESP issued Opinions related to i) the methodological quality of economic evidence and ii) the cost-effectiveness and budget impact of the drugs under review.ResultsThe estimated incremental cost-utility ratio (ICUR) of tisagenlecleucel were rejected, being based on insufficient clinical evidence to estimate and extrapolate the long-term progression and to compare tisagenlecleucel with alternatives. Thus, the CEESP concluded that tisagenlecleucel was not proved cost-effective. The estimated ICUR of axicabtagene ciloleucel at 114,509EUR/QALY vs. chemotherapies was associated with an acceptable level of evidence despite being based on a frail indirect comparison and limited data on quality of life. In a context where France has no official cost-effectiveness threshold, the CEESP considered axicabtagene ciloleucel ICUR to be “very high” and questioned the collective acceptability of the claimed price.The CEESP stressed that the main source of uncertainty surrounding the ICUR estimates of both drugs was related to the lack of hindsight on effectiveness, especially in terms of overall survival and safety.ConclusionsThe economic evaluation of CAR-T cell therapies highlights the sources of uncertainty underlying the decision and the risk of inefficient resource allocation driven by limited clinical data. It calls for payment schemes accounting for the uncertainty, and effective collection of relevant post-marketing data.

Challenges raised by the economic evaluation of CAR-T-cell therapies. The review by the French National Authority for Health

2021 ◽  
Author(s):  
Véronique Raimond ◽  
Emmanuelle Kaltenbach ◽  
Christophe Adam ◽  
Sébastien Lazzarotto ◽  
Catherine Le Galès ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
T Cell ◽  
National Authority ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T

scholarly journals How should we evaluate the cost-effectiveness of CAR T-cell therapies?

2020 ◽  
Vol 9 (3) ◽  
pp. 271-273
Author(s):  
Nishma Patel ◽  
Suzanne S. Farid ◽  
Stephen Morris
Keyword(s):  
Cost Effectiveness ◽  
T Cell ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T ◽  
The Cost

scholarly journals Cost-Effectiveness of Lisocabtagene Maraleucel (liso-cel) Versus Axicabtagene Ciloleucel (axi-cel) for Treatment of Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3003-3003
Author(s):  
Christopher Parker ◽  
Fei Fei Liu ◽  
Kristen Deger ◽  
Conrado Franco-Villalobos ◽  
Irina Proskorovsky ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
T Cell ◽  
Cost Savings ◽  
Cost Effective ◽  
Publicly Traded ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background: Patients with R/R LBCL after primary treatment have historically had a poor prognosis and few treatment options. Prior research found that the chimeric antigen receptor (CAR) T cell therapy, axi-cel may be cost-effective in comparison with salvage chemotherapy. Liso-cel, a CD19-directed CAR T cell therapy, may have comparable survival and a better safety profile than axi-cel, representing a valuable treatment option in CD19-directed CAR T cell therapy. We developed an economic model assessing cost-effectiveness of liso-cel versus axi-cel for patients with R/R LBCL after ≥ 2 lines of therapy from a commercial United States (US) payer perspective. Methods: Patients entered the model at leukapheresis and were subsequently stratified according to their pre-infusion experience (ie, whether or not they received the CAR T cell infusion due to death or other reasons). The model used a partitioned survival approach to estimate health state occupancy (progression-free survival [PFS], progressive disease, and death) and calculate incremental cost-effectiveness ratios using life-years and quality-adjusted life-years (QALY) over a lifetime horizon. Survival curves from clinical trials of CAR T cell therapies in R/R LBCL exhibit a plateau, indicating a fraction of patients may achieve durable remission after treatment. Parametric survival models that incorporate cure assumptions or hazards that converge to general population mortality have been widely accepted in R/R LBCL by health technology assessment bodies for CAR T cell therapies. Parametric mixture-cure modeling was used to extrapolate overall survival (OS) and PFS data from TRANSCEND NHL 001 (TRANSCEND [NCT02631044]) for liso-cel and ZUMA-1 (NCT02348216) for axi-cel. Survival of cured patients was modeled per the age- and sex-adjusted general population, adjusted by an excess mortality risk. Survival of non-cured patients was estimated using parametric distributions. Given meaningful differences in the study design, eligibility criteria, and baseline patient characteristics between the two trials, comparative efficacy (OS, PFS) and safety (adverse events [AE]) were estimated using matching-adjusted indirect comparison (MAIC). EQ-5D-5L data from TRANSCEND were used to estimate utilities for health states and AEs. Costs included pretreatment (leukapheresis, bridging therapy, and lymphodepleting chemotherapy), acquisition and administration of CAR T-cell therapies and subsequent-line treatments, all-grade AE management, post-infusion hospitalization, monitoring, and end-of-life care. Uncertainty was examined using sensitivity and scenario analyses. Scenarios matching TRANSCEND with ZUMA-1 on bridging therapy and assuming all patients received the CAR T cell infusion were also conducted to explore the impact of potential bias resulting from trial design differences. Results: Following matching and adjustment, the liso-cel effective sample size for indirect comparison was 99 patients. Patients receiving liso-cel achieved improved 5-year survival compared with axi-cel (45% vs 41%, respectively). In the base case, liso-cel dominated axi-cel with nearly equivalent QALYs (0.02) and cost savings of $75,063 (Table 1). The favorable safety profile of liso-cel, including lower rates of cytokine release syndrome and neurological events, was reflected in cost savings (−$35,464) and QALY gains (0.05) when compared with axi-cel. In probabilistic sensitivity analyses, the probability that liso-cel was more effective and less costly than axi-cel was 52% and the probability that liso-cel was cost-effective at a threshold of $100,000 was 78%. Key drivers of cost-effectiveness included the OS cure fraction and the percent of patients experiencing grade 3/4 AEs for axi-cel (Figure). Additionally, 2 scenarios that sought to adjust for differences in trial design both predicted QALY gains and cost savings for liso-cel versus axi-cel (Table 2). Conclusions: This analysis estimated that liso-cel is cost-effective compared with axi-cel from a commercial US payer perspective, generating similar QALYs at lower cost, partly owing to a favorable safety profile associated with liso-cel. Figure 1 Figure 1. Disclosures Parker: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Liu: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Franco-Villalobos: Bristol Myers Squibb: Consultancy; Other pharmaceutical companies: Consultancy. Proskorovsky: Evidera: Current Employment. Keating: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

OP206 Expert Elicitation Of Probabilistic Distributions to Inform Survival Modelling of CD19 Chimeric Antigen Receptor T-Cell Therapies

2020 ◽  
Vol 36 (S1) ◽  
pp. 3-3
Author(s):  
Niamh Carey ◽  
Conor Hickey ◽  
Laura Mc Cullagh ◽  
Michael Barry
Keyword(s):  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Expert Elicitation ◽  
Cell Transplant ◽  
Major Advance ◽  
Cell Therapies ◽  
Risk Of Death ◽  
Car T Cell ◽  
Car T

IntroductionIn 2018, the National Centre for Pharmacoeconomics (NCPE) was commissioned to conduct a health technology assessment (HTA) of one of the first commercially available chimeric antigen receptor (CAR) T-cell therapies, tisagenlecleucel. CAR T-cells are a major advance in personalized cancer treatment, demonstrating promising outcomes in relapsed/refractory pediatric acute lymphoblastic leukemia (pALL). However, the results are based on short-term follow up, limiting their value in predicting long-term survival and leading to uncertainty about the most appropriate survival modeling method to employ. This study aimed to address these limitations by means of expert elicitation.MethodsAn expert elicitation method, the histogram technique, was employed. A predefined discrete numerical scale was presented in Microsoft Excel® and the expert was asked to place twenty crosses on a frequency chart. These crosses represented the expert's beliefs about the distribution of particular quantities. Each cross represented five percent of the probabilistic distribution. Individual distributions were then aggregated across experts using linear pooling.ResultsA total of seventeen experts were invited to take part; eight agreed to participate and five completed the exercise. Three experts did not consider tisagenlecleucel to be a “curative” therapy because patients had a higher risk of death, compared with the age- and sex-matched general population. The aggregated distributions indicated the five-year overall survival rate to be thirty-three percent (95% CI 8.65–56.88) in patients who do not receive a subsequent stem cell transplant and twenty percent (95% CI 2.38 -52.04) in those who do.ConclusionsThe results of this study will be used to calibrate CD19 CAR T-cell therapy survival estimates presented in HTA submissions to the NCPE to ensure more robust assessments. They will also be used to inform the construction of a de novo cost-utility model for examining the cost effectiveness of CD19 CAR T-cell therapies for relapsed/refractory pALL in the Irish healthcare setting.

scholarly journals Immunotherapy using IgE or CAR T cells for cancers expressing the tumor antigen SLC3A2

2021 ◽  
Vol 9 (6) ◽  
pp. e002140
Author(s):  
Giulia Pellizzari ◽  
Olivier Martinez ◽  
Silvia Crescioli ◽  
Robert Page ◽  
Ashley Di Meo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
T Cells ◽  
T Cell ◽  
Type I ◽  
Cell Therapies ◽  
Car T Cells ◽  
Car T Cell ◽  
Tumor Associated Antigen ◽  
Car T

BackgroundCancer immunotherapy with monoclonal antibodies and chimeric antigen receptor (CAR) T cell therapies can benefit from selection of new targets with high levels of tumor specificity and from early assessments of efficacy and safety to derisk potential therapies.MethodsEmploying mass spectrometry, bioinformatics, immuno-mass spectrometry and CRISPR/Cas9 we identified the target of the tumor-specific SF-25 antibody. We engineered IgE and CAR T cell immunotherapies derived from the SF-25 clone and evaluated potential for cancer therapy.ResultsWe identified the target of the SF-25 clone as the tumor-associated antigen SLC3A2, a cell surface protein with key roles in cancer metabolism. We generated IgE monoclonal antibody, and CAR T cell immunotherapies each recognizing SLC3A2. In concordance with preclinical and, more recently, clinical findings with the first-in-class IgE antibody MOv18 (recognizing the tumor-associated antigen Folate Receptor alpha), SF-25 IgE potentiated Fc-mediated effector functions against cancer cells in vitro and restricted human tumor xenograft growth in mice engrafted with human effector cells. The antibody did not trigger basophil activation in cancer patient blood ex vivo, suggesting failure to induce type I hypersensitivity, and supporting safe therapeutic administration. SLC3A2-specific CAR T cells demonstrated cytotoxicity against tumor cells, stimulated interferon-γ and interleukin-2 production in vitro. In vivo SLC3A2-specific CAR T cells significantly increased overall survival and reduced growth of subcutaneous PC3-LN3-luciferase xenografts. No weight loss, manifestations of cytokine release syndrome or graft-versus-host disease, were detected.ConclusionsThese findings identify efficacious and potentially safe tumor-targeting of SLC3A2 with novel immune-activating antibody and genetically modified cell therapies.

scholarly journals Potential strategies against resistance to CAR T-cell therapy in haematological malignancies

2020 ◽  
Vol 12 ◽  
pp. 175883592096296
Author(s):  
Qing Cai ◽  
Mingzhi Zhang ◽  
Zhaoming Li
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Haematological Malignancies ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigen receptor (CAR) T-cell therapy is a rapidly developing method for adoptive immunotherapy of tumours in recent years. CAR T-cell therapies have demonstrated unprecedented efficacy in the treatment of patients with haematological malignancies. A 90% complete response (CR) rate has been reported in patients with advanced relapse or refractory acute lymphoblastic leukaemia, while >50% CR rates have been reported in cases of chronic lymphocytic leukaemia and partial B-cell lymphoma. Despite the high CR rates, a subset of the patients with complete remission still relapse. The mechanism of development of resistance is not clearly understood. Some patients have been reported to demonstrate antigen-positive relapse, whereas others show antigen-negative relapses. Patients who relapse following CAR T-cell therapy, have very poor prognosis and novel approaches to overcome resistance are required urgently. Herein, we have reviewed current literature and research that have investigated the strategies to overcome resistance to CAR T-cell therapy.

CAR T-Cell Therapies in Glioblastoma: A First Look

2017 ◽  
Vol 24 (3) ◽  
pp. 535-540 ◽  
Author(s):  
Denis Migliorini ◽  
Pierre-Yves Dietrich ◽  
Roger Stupp ◽  
Gerald P. Linette ◽  
Avery D. Posey ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T

An Overview of Multiplexed Analyses of CAR T-cell Therapies: Insights and Potential

2021 ◽  
Author(s):  
Brittany Paige DePriest ◽  
Noah Vieira ◽  
Alan Bidgoli ◽  
Sophie Paczesny
Keyword(s):  
T Cell ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T

scholarly journals Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel–treated patients in the TRANSCEND NHL 001 trial

2021 ◽  
Vol 5 (6) ◽  
pp. 1695-1705
Author(s):  
Jeremy S. Abramson ◽  
Tanya Siddiqi ◽  
Jacob Garcia ◽  
Christine Dehner ◽  
Yeonhee Kim ◽  
...  
Keyword(s):  
Health Care ◽  
T Cell ◽  
B Cell Lymphoma ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
System Perspective ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T ◽  
Grade 3

Abstract Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell–specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

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