Tisagenlecleucel (chimeric antigen receptor T-cells targeting CD19) for patients with relapsed/refractory B-cell acute lymphoblastic leukemia: asystematic review and cost-utility analysis from a Spanish perspective

Abstract

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) have a poor prognosis with conventional therapies. In the summer of 2018, the European Medicines Agency approved tisagenlecleucel (tisa-cel, Kymriah®, Novartis), for the treatment of these patients based on a single-arm phase 2 international clinical trial with a short follow-up. The price tag for this product is €320,000 but under a pay-for-performance scheme in which the health care provider pays €192,000 upfront and the other €128,000 if the patient is alive and in remission 18 months later. The main objective of this study was to perform a costutility analysis of tisa-cel from a Spanish point of view. Tisa-cel resulted in a longer life expectancy (9.89 LYs) than the other two therapies evaluated (6.45 and 1.94 LYs for blinatumomab and clofarabine, respectively). The difference in relapse-free survival (RFS) led to 3.75 additional QALYs for patients receiving tisa-cel compared to blinatumomab at a cost of €55,779/QALY, and 7,15 additional QALYs compared to clofarabine at a cost of €35,787/QALY. The Markov process revealed very similar results: the difference in RFS resulted in 3.67 additional QALYs for tisa-cel compared to blinatumomab at a cost of €57,368/QALY (95% confidence interval [CI]: 52,779-61,956), and 7.3 additional QALYs compared to clofarabine at a cost of €35,504/QALY (95% CI: 35,153-35,854). One-way sensitivity analyses showed that the factor that had the greatest impact on the cost-effectiveness of tisa-cel (over blinatumomab) was its cost. In conclusion, tisa-cel could be considered costeffective in the treatment of patients with R/R pediatric ALL when the WTP threshold is set at €50,000/QALY (or higher), but many uncertainties remain (lack of comparative data, short follow-up).