Pomalidomide Plus Low-Dose Dexamethasone (POM + LoDEX) for Relapsed and Refractory Multiple Myeloma (RRMM): Results from a Pharmacoeconomic Evaluation
Authors: Schey Steve , Dhanasiri Sujith , Lee Dawn , Sternas Lars , Yu Xin , Zaki Mohamed H. , Elvidge Jamie , O'Dwyer Michael 
Published: November 2019

Abstract
Background: Multiple myeloma remains an incurable disease, placing a significant burden on patients (pts), families, and healthcare systems. Bortezomib (BORT) and IMiDs® immunomodulatory agents (thalidomide and lenalidomide [LEN]) have improved progression-free survival (PFS), time to progression, and overall survival (OS). However, over time, nearly all pts become refractory which greatly impacts prognosis (median OS, 3-9 mos). In the absence of approved treatments, guidelines recommend clinical trials or retreatment with agents that were previously effective, but published data in the appropriate pt population for current care (CC) options are limited to those from small, observational, early-phase studies. There is a need for newer effective treatments; however, access is increasingly being determined by the demonstration of both clinical and economic value. POM + LoDEX demonstrated a significant OS benefit vs. high-dose dexamethasone (HiDEX) in the pivotal phase 3 MM-003 study (San Miguel, Lancet Oncol, 2013). POM + LoDEX has EU approval in RRMM pts in whom BORT and LEN failed.
Objective: Explore the cost-effectiveness of POM + LoDEX vs. CC from a UK and Ireland healthcare payer perspective.
Methods: A de novo pharmacoeconomic evaluation was conducted to compare costs and outcomes of POM + LoDEX to CC in the UK and Ireland. CC included BORT retreatment (intravenous [IV] or subcutaneous), LEN (oral), and bendamustine (IV) regimens. Efficacy data were sourced from MM-003 and 2 observational studies: a dataset for CC (Gooding, 2013; n = 30 pts primarily treated with BORT, bendamustine, or LEN; 100% received prior BORT and LEN) and a dataset for BORT + LEN (Jimenez-Zepeda, 2013; n = 30, 80% received prior BORT, 73% prior LEN). Validation of the approach and all model assumptions was achieved through extensive clinical and health economic expert consultation and by comparing comparator arm outcomes from observational data to the MM-003 (HiDEX) control arm data. The health economic model used a partitioned survival structure with OS and PFS parametric curves fitted to the datasets to estimate the number of pts at each time point expected to be preprogression, postprogression, or dead. Time to treatment failure curves were estimated to allow treatment discontinuation modelling. EQ-5D data, collected as part of MM-003, were used to inform quality of life (QOL) weights. A utility regression equation was developed to account for important covariates and allow utility to vary over time. The economic evaluation included the cost of treatment, administration, monitoring, tests, adverse events (AEs), blood transfusions, concomitant medication, and terminal care. Costs are presented in US dollars using an exchange rate of 0.74 per € and 0.58 per £. Costs and outcomes were modeled to estimate cost per life year (LY) and cost per quality-adjusted life year (QALY) gained over a lifetime horizon.
Results: In the base-case analysis, POM + LoDEX was associated with a total incremental cost of $59,250 per pt over a lifetime horizon compared with CC (Table 1). Pts who receive POM + LoDEX are predicted to live for a mean of 2.2 years, compared with 1.2 years with CC. This represents an additional 0.6 QALYs. The model predicts a deterministic incremental cost-effectiveness ratio (ICER) of $100,920/QALY compared with CC, while the probabilistic ICER obtained through 1000 probabilistic model runs was consistent at $101,947/QALY.
Table 1 : Base-Case Cost-Effectiveness Results Model Results POM + LoDEX CC Difference Clinical outcomes Median OS, mos 12.7 5.5 7.2 Mean predicted life-years (over a pt lifetime) 2.2 1.2 1.0 QALYs 1.3 0.7 0.6 Cost outcomes, US dollars Medication and administration $84,698 $29,880 $54,818 Monitoring $8230 $4489 $3741 AE management (outpatient visits and hospitalization) $7135 $6444 $691 Total $100,063 $40,813 $59,250 ICER—Cost/LY $58,112 ICER—Cost/QALY $100,920
Conclusion: There are limited alternative treatment options available in the UK and Ireland for RRMM pts. None have a proven effect on survival leaving pts to face potentially ineffective retreatments. End-of-life drugs that significantly improve survival and QOL and address unmet need can be considered to be cost-effective at a higher “willingness to pay” threshold. POM, an oral therapy with significant PFS, survival, and QOL with a known safety profile, is likely to be a cost-effective use of healthcare resources.

Disclosures
Dhanasiri: Celgene Corp: Employment, Equity Ownership. Lee:Celgene Corp: Consultancy. Sternas:Celgene Corp: Employment, Equity Ownership. Yu:Celgene Corp: Employment, Equity Ownership. Zaki:Celgene Corp: Employment, Equity Ownership. Elvidge:Celgene Corp: Consultancy.