Tisagenlecleucel for the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukaemia in People Aged up to 25 Years: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

• Published in: PharmacoEconomics 2019-10, Vol.37 (10), p.1209-1217
• Main Authors: Walton, Matthew, Sharif, Sahar, Simmonds, Mark, Claxton, Lindsay, Hodgson, Robert
• Format: Article
• Language: English
• Subjects: Acute lymphocytic leukemia; Age; Antigens; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - economics; Chemotherapy; Child; Clinical trials; Committees; Cost analysis; Cost-Benefit Analysis; Data collection; Drug therapy; Economic aspects; Health Administration; Health Economics; Health services; Health technology assessment; Humans; Leukemia; Medical prognosis; Medicine; Medicine & Public Health; Models, Economic; Patients; Pediatrics; Pharmaceutical industry; Pharmacoeconomics and Health Outcomes; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - economics; Product development; Public Health; Quality of Life Research; Quality-Adjusted Life Years; Receptors, Antigen, T-Cell - administration & dosage; Review Article; Survival; Survival Analysis; Technology Assessment, Biomedical; Young Adult; Young adults
• ISSN: 1170-7690; 1179-2027
• DOI: 10.1007/s40273-019-00799-0

As part of the National Institute for Health and Care Excellence’s (NICE’s) Single Technology Appraisal (STA) process, Novartis submitted evidence on the clinical effectiveness and cost-effectiveness of tisagenlecleucel for treating paediatric and young adult patients (under the age of 25 years) with relapsed or refractory (r/r) B-cell acute lymphoblastic leukaemia (ALL). This article presents a summary of the Evidence Review Group’s (ERG’s) independent review of the evidence submission, the committee’s deliberations, and the subsequent development of NICE guidance for the use of tisagenlecleucel on the National Health Service (NHS) in England. Tisagenlecleucel is a chimeric antigen receptor-modified T-cell (CAR-T) product, the first of this emerging therapeutic class to be considered by NICE in this indication. The company’s evidence submission was based upon three single-arm, phase II studies: ELIANA, ENSIGN, and B2101J. These trials demonstrated a beneficial effect of tisagenlecleucel, with significant extensions in event-free survival (EFS) and overall survival (OS) compared to historical control datasets on blinatumomab and salvage chemotherapy. Adverse events were common; 77% of patients suffered from cytokine release syndrome (CRS), 56% of whom required intensive care unit-level care. The ERG did not consider clofarabine monotherapy an appropriate proxy for salvage chemotherapy. The company presented a hybrid cost-effectiveness model, combining a decision tree and three-state partitioned survival model structure. The majority of quality-adjusted life-years (QALYs) gained were generated through additional life-years in the extrapolated ‘long-term survival’ phase of the model, where patients were assumed to be ‘cured’. The ERG considered the results to be subject to substantial uncertainty, due in part to immature trial data, unresolved long-term treatment effects, and a lack of appropriate comparator data. The ERG implemented a number of changes to the company’s model in an alternative base case, producing deterministic incremental cost-effectiveness ratios (ICERs) of £45,397 per QALY gained versus salvage chemotherapy, and £27,732 versus blinatumomab. The probabilistic model produced ICERs of £48,265 per QALY gained versus salvage chemotherapy, and £29,501 versus blinatumomab. The committee considered the ERG’s analysis to be most closely aligned with their preferred assumptions, and did not consider tisagenlecleucel to meet both of the end-of-life