Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Pediatric B-Cell Acute Lymphoblastic Leukemia

Abstract

Purpose The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel was recently approved to treat relapsed or refractory pediatric acute lymphoblastic leukemia. With a one-time infusion cost of $475,000, tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to determine whether tisagenlecleucel is cost effective compared with currently available treatments. Methods Markov modeling was used to evaluate tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia from a US health payer perspective over a lifetime horizon. The model was informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel (under a range of plausible long-term effectiveness) was compared with blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic sensitivity analyses were used to explore uncertainty. Main outcomes were life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Results With an assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5-year relapse-free survival rate, life-expectancies were more modest (3.8 years) and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate and with use as a bridge to transplant, tisagenlecleucel increased life expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios. Conclusion The long-term effectiveness of tisagenlecleucel is a critical but uncertain determinant of its cost effectiveness. At its current price, tisagenlecleucel represents reasonable value if it can keep a substantial fraction of patients in remission without transplantation; however, if all patients ultimately require a transplantation to remain in remission, it will not be cost effective at generally accepted thresholds. Price reductions would favorably influence cost effectiveness even if long-term clinical outcomes are modest.

CAR T Cell Generation by piggyBac Transposition from Linear Doggybone DNA Vectors Requires Transposon DNA-Flanking Regions

“…2-15 However, their widespread application is limited, in part, by the cost and complexity of production processes utilizing viral vectors. 16 Transposon systems are nonviral vectors that are traditionally plasmid based and provide the opportunity to significantly reduce the cost of CAR T cell production. Both the piggyBac and Sleeping Beauty transposon systems have been used to generate CAR19 T cells that have potent activity against B cell malignancies.…”

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15] The cost of CAR T cell production remains a major barrier to their widespread use. 16 Most CAR T cells to date have been produced using g-retroviral or lentiviral transduction. The generation of these vectors is expensive, and the availability of vector at clinical grade is a major barrier to widespread implementation of CAR T cell therapy, a problem that will worsen as demand increases when effective CAR T cell therapies are developed for common cancers.…”

A systematic review of economic evaluations of advanced therapy medicinal products

“…The main methodological challenge was the lack of clinical data with which to inform any modelling or economic evaluation attempted. 12,14,18,20,22,24,25,27,28 In all these studies, the problem was (2018) 19 estimated the time at which long-term survivors would be considered effectively cured based on assumptions that were necessary to extrapolate the survival curve for trial participants. While disease modelling provides a way of estimating long-term effects, this does not substitute for good quality clinical trial evidence.…”

“…In terms of reporting, 13 studies 13,14,[18][19][20][21][22]25,27,29,30,33 were deemed to be of good quality (see Supplementary Appendix S1). However, many were incomplete with respect to important methodological detail.…”

Driving CAR T cell translation forward

“…The prices for these products are high, at $373,000 per product for axicabtagene ciloleucel and $475,000 for tisagenlecleucel. Although CAR T cells in ALL can at times replace stem cell transplantation, CAR T cell therapy is often used as a bridge to transplant, incurring the costs of both therapies (10). It is anticipated that improvements in the manufacturing process and reductions in the cost of goods may ultimately result in lower prices and support scalability.…”