The Economic Value of CTL019 Therapy for Pediatric Patients with Relapsed and Refractory Acute Lymphoblastic Leukemia in the United Kingdom

Introduction: Pediatric B-cell acute lymphoblastic leukemia (pALL) affects approximately 400 new patients in the United Kingdom (UK) each year (Pediatric Blood & Cancer 2017;00:e26615). With current therapies, approximately 80% of patients achieve remission; however treatment options are limited for those who relapse or do not respond to salvage therapy (World J Hematol. 2014;3:3). Novel personalized treatments currently under development, such as CTL019, may provide a safe and efficacious therapeutic option for these patients. The National Institute for Health and Care Excellence (NICE) recently conducted a cost-effectiveness analysis that modeled the benefits relative to the costs using early CTL019 trial data (Health Technol Assess. 2017;21:7). This study expands upon that analysis to investigate the potential economic benefit of CTL019 to patients.

Methods: To quantify the economic value of CTL019 for patients compared to standard of care (clofarabine) in the UK, we expanded upon the NICE model and demonstrated the economic value of the incremental quality adjusted life years (QALYs) gained for 10 incident cohorts. NICE reported that there are 38 incident cases of relapsed and refractory pALL in patients under 30 years old annually based on an estimated 20% of patients who experience a relapse and 50% who do not respond to salvage therapy (Health Technol Assess. 2017;21:7). We first obtained estimates of the size of the patient population, life expectancy, QALYs, and healthcare costs from the curative intent scenario of the NICE model. As in the NICE report, we calculated the economic value of the patients' health gains by valuing each QALY gained at £50,000. Other costs including conditioning, hospitalizations, adverse events, hematopoietic stem cell transplantation and follow-up costs were also included in the analysis. We discounted all health and monetary values at a rate of 3.5% and inflated all costs to 2016 Great Britain pounds. Building on the NICE model, we calculated the patients' expected productivity using nationally representative data on employment rates and earnings by age and sex from the Office of National Statistics. Productivity differences were determined primarily by differences in expected survival between patients on CTL019 and clofarabine. Finally, we calculated the consumer surplus accruing to patients from the use of CTL019 using three pricing scenarios considered in the NICE publication: £250,000, £356,100 and £528,600. Consumer surplus is an economic concept that measures the difference between how much a consumer is willing to pay for a good or service, and its price; the more the consumer is willing to pay for a good in excess of its price, the higher the consumer surplus.

Results: Aligning with the NICE report, our study population included 380 patients under age 30 with relapsed or refractory pALL. Specifically, patients gained an additional 3,294 cumulative QALYs (an average of 10.1 QALYs per patient in each cohort) from CTL019 treatment relative to clofarabine. Based on our additional analysis, these QALY gains translated to £164,690,866 of total value, of which £49,525,920 are attributable to added patient productivity from employment gains. Using the three prices considered by NICE, £250,000; £356,100; and £528,600, we found that the consumer surplus accruing to patients is £91,847,131; £57,142,661; and £719,276, respectively. This amounts to an average of £280,799 £174,699 and £2,199 of consumer surplus accruing to each patient.

Conclusions: Innovative therapies such as CLT019 have the potential to provide significant benefit to patients and society in the UK. In particular, patients receiving CTL019 therapy are expected to experience meaningful improvements in life expectancy and QALYs. In addition to their inherent value, these gains will extend patients' potential working lives, enabling them to contribute to UK productivity. Though the magnitude of consumer surplus accruing to patients will depend upon the CTL019's price on approval, our analysis demonstrates that consumers will derive a large benefit at a wide range of prices. Further research is needed to demonstrate the societal value of CTL019 by incorporating additional components into the analysis such as reduced caregiver burden from one time treatments and producer profits.