## Abstract

Introduction

The effectiveness of bortezomib for induction treatment prior to ASCT in multiple myeloma (MM) patients has been demonstrated in a number of randomized, open-label phase III trials, including the IFM 2005-01 trial (Harousseau et al., J Clin Oncol 2010;28(30):4621-9). This trial showed that the addition of bortezomib as part of an induction treatment prior to ASCT resulted in statistically significant improvements in post-induction response rates and longer progression-free survival (PFS) compared to a non-bortezomib containing regimen (NBCR). The objective of this study was to assess the cost-utility of a bortezomib-containing regimen (BCR) vs. a NBCR for induction treatment in previously untreated MM patients prior to ASCT from a Canadian public payer perspective, based on the results of the IFM 2005-01 study.

Methods

A Markov model was developed to estimate the cost-utility over a lifetime horizon (50 years) in previously untreated MM patients undergoing induction and ASCT. The model simulated disease progression of patients with previously untreated MM through three health states: “progression-free”, “progression” and “death”, with all patients beginning in the progression-free state. The PFS and overall survival (OS) curves from the IFM 2005-01 trial were extrapolated beyond the study follow-up period to estimate the timeframe spent in each health state. Each health state was associated with a utility value and direct medical costs. Utilities for the progression-free and progression health states were derived from a previous cost-utility analysis for bortezomib and were 0.81 and 0.645, respectively (Hornberger et al., Eur J Haematol 2010;85(6):484-91). Transition probabilities between health states were estimated by calibrating the model to the PFS and OS curves from the IFM 2005-01 trial. In the base case, transition probabilities beyond the trial follow-up period were conservatively assumed to be equal for both treatment groups. Medical resource utilization was estimated using the IFM 2005-01 trial, and supplemented by published literature and clinical advisors. Clinical advisors also provided input on management of adverse events (> grade 3) and treatment of patients who progressed after induction and ASCT. Resource costs were estimated using Canadian sources ($CAN 2012) and costs and outcomes were discounted at 5% annually. Because patients in each group incurred similar costs (i.e. cost of an ASCT), only incremental costs between the two arms were included in the analysis. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to test the robustness of the model. Results The mean total MM-related cost over the lifetime analysis in the model was$68,800 per patient treated with a BCR and $47,000 per patient treated with a NBCR. Addition of bortezomib to the induction regimen increased costs by$21,700 (see table). Over the model lifetime, a delay in progression with a BCR led to 0.25 years of additional survival compared to a NBCR and a quality-adjusted life-year (QALY) gain of 0.22 years. The incremental cost-utility ratio for induction using a BCR compared to a NBCR approach was $99,200/QALY. Sensitivity analyses identified the major factors impacting the cost-utility ratio as: transition probabilities beyond the trial follow-up period, discounting, utilities and bortezomib costs. The probability of a BCR being cost-effective compared to a NBCR was 43.9% at a threshold of$100,000/QALY.

Conclusions

A number of phase 3 trials have demonstrated the effectiveness of bortezomib as part of an induction regimen prior to ASCT. This analysis indicates that, from a Canadian perspective, induction treatment with a BCR in previously untreated MM patients prior to ASCT can be cost-effective at conventional decision thresholds with a cost-utility ratio of $99,200/QALY. Disclosures: Kouroukis:Janssen Inc.: Honoraria. White:Janssen Inc.: Consultancy, Honoraria. Kruse:OptumInsight: Employment. Lawrence:OptumInsight: Employment. Trambitas:Janssen Inc.: Employment. Table 1 Lifetime cost-effectiveness results TreatmentTotal CostsTotal LYs*Total QALYsΔCostsΔLYsΔQALYsCost per LY savedCost per QALY gained NBCR$47,000 6.54 4.80 -- -- -- Ref Ref
BCR $68,800 6.79 5.02$21,700 0.25 0.22 $88,600$99,200
TreatmentTotal CostsTotal LYs*Total QALYsΔCostsΔLYsΔQALYsCost per LY savedCost per QALY gained
NBCR $47,000 6.54 4.80 -- -- -- Ref Ref BCR$68,800 6.79 5.02 $21,700 0.25 0.22$88,600 \$99,200
*

LYs, life-years

## Author notes

*

Asterisk with author names denotes non-ASH members.