Cost-Effectiveness of Lenalidomide in Multiple Myeloma Patients with 1 Prior Therapy in England and Wales,

Lenalidomide plus dexamethasone (Len+Dex) is approved by EMA for patients with multiple myeloma (MM) who have received at least 1 prior therapy. In the wake of NICE's guidance on Thalidomide and Bortezomib TA 228 for 1^st-line treatment of MM, Len+Dex may be the only available novel therapy option with potential to extend survival beyond traditional therapies for patients failing the NICE recommended initial treatments; thalidomide or bortezomib both in combination with melphalan and prednisone. Therefore, economic modelling was undertaken to evaluate the cost-effectiveness of Len+Dex from the perspective of the National Health Service (NHS), England and Wales.

An Excel-based individual simulation model was developed to account for disease history which affects time-to-progression (TTP) and overall survival (OS) in relapse refractory MM patients. The OS for each individual within the model was calculated as the combination of that patient's TTP and post progression survival (PPS). The TTP efficacy was derived from a subgroup analysis of patients from the MM-009/010 pivotal trials who had received only 1 prior therapy. The derived equation for TTP included parameters for treatment response, Len+Dex treatment effect and certain baseline characteristics of patients with only 1 prior therapy. The PPS for patients within the model was also derived from the MM-009/010 trials; however, since 47% of patients on Dex switched to Len+Dex at progression, there was a significant Len+Dex effect in the Dex PPS. To account for this, the Dex PPS was calibrated using the longer follow up from the UK Medical Research Council (MRC) trials. Resource use for monitoring and adverse events was obtained via a survey of expert hematologists in the UK. Costs were taken from NHS sources and included a Patient Access Scheme where patients received Len free of charge beyond 26 cycles of use. Utility values were taken from published literature and applied to patients prior to progression (based on their best response rate achieved) and after progression. The robustness of the model results were assessed by sensitivity analyses whereby individual model parameters were varied across their confidence intervals (CI). Results reported include life-years (LY), quality-adjusted life-years (QALY), costs, cost per LY gained and cost per QALY gained. NICE technology appraisal methodology guidelines were followed when modelling over a lifetime horizon and applying a 3.5% discount rate for future benefits and costs. All costs presented are in British pounds.

Len+Dex had a substantial increase in health-related outcomes compared to Dex alone, with LYs of 5.37 vs. 2.15 and QALYs of 3.69 vs. 1.49, respectively. The associated drug costs for Len+Dex over the patients' lifetime were higher: however, survival benefits accrued over the same time period offset the cost differences between the two regimens, resulting in a cost per LY gained of 20,639 and per QALY gained of 30,153. The model results remained robust to sensitivity analysis conducted on most parameters and utility estimates. The only parameter that affected the results was the adjustment factor for Dex survival when varied across its 95% CI (see table).

These results indicated that Len+Dex at 2^nd line is cost-effective for a novel drug in an orphan disease compared to Dex alone. Despite Len+Dex only being recommended by NICE for use in MM patients with 2 or more prior therapies (with the recent NICE decision to allow thalidomide and Velcade in de novo patients), treatment alternatives for 2^nd line therapy with novel agents is more limited. It is important for clinicians to consider the costs and benefits of 2^nd line therapy. This analysis demonstrated that Len+Dex is cost-effective for 2^nd line patients and meets the commonly quoted cost per QALY threshold of 30,000.

Schey:Celgene: Consultancy. Stern:United BioSource Corporation: Employment; Celgene: Consultancy. Dhanasiri:Celgene: Employment. Brown:United BioSource Corporation: Employment; Celgene: Consultancy.