Abstract
Background: Induction therapy for multiple myeloma (MM) patients who are eligible for autologous stem cell transplant (ASCT) has evolved with the introduction of novel agents, such as bortezomib (VELCADE®, Vel) and thalidomide (THALOMID®, Thal). Phase 3 trial data show the clinical effectiveness of front-line bortezomib-based therapies, but little is known about the comparative economic benefit of bortezomib-based regimens in newly diagnosed MM in the transplant setting. Here we report a pharmacoeconomic analysis of the IFM 2005-01, GIMEMA MMY-3006, and the Myeloma-Autogreffe Group (MAG) phase 3 trials, comparing the relative costs of Vel–dexamethasone (Vel/Dex), vincristine–doxorubicin–dexamethasone (VAD), Vel–Thal–Dex (VTD), and Thal–Dex (TD).
Methods: Expanding on a previous budget impact model of bortezomib treatment for relapsed MM (Fullerton et al. Blood2007: Abstract 3324), an Excel-based model was developed to calculate the cost of therapy for MM patients eligible for ASCT, including costs incurred during induction therapy and single or double transplant. Per IFM 2005-01 protocol design, we assumed that patients who achieved at least very good partial response (≥VGPR) after their first transplant did not need a second transplant; the GIMEMA and MAG trials were based on a similar tandem transplant protocol. Costs were evaluated from a health system perspective and included: induction therapy costs (drugs, medical care, adverse events [AEs], and prophylaxis treatment), cost of the first ASCT, and cost of the second ASCT if required. Drug costs were calculated based on 2008 Average Wholesale Price and applied to trial regimens. Medical care costs were based on the Medicare physician fee schedule and assumptions drawn from National Comprehensive Cancer Network (NCCN) MM treatment guidelines. AE costs (grade ≥3 AEs reported in at least two studies) were estimated using available incidence data and reported as per-event costs or annual costs depending on the data source. The unit cost of a transplant ($139,220) was calculated based on data from 1,917 MM patients treated at >120 centers in the OptumHealth database.
Results: In IFM 2005-01, estimated mean per-patient treatment costs from start of induction to completion of second transplant (if required) were lower for patients receiving Vel/Dex induction ($201,793) versus VAD ($217,526), due to better post-induction response with Vel/Dex. More patients achieved post-transplant ≥VGPR with Vel/Dex than with VAD (72% vs 52%), and therefore did not require a second transplant. Similarly, in GIMEMA MMY-3006, post-induction and posttransplant ≥VGPR achieved with VTD induction was greater than that achieved with TD (post-induction: 60% vs 27% and post-transplant: 77% vs 54%), thereby reducing the need for a second transplant among patients receiving VTD induction therapy. Consequently, estimated mean treatment costs were lower for patients receiving VTD induction ($200,093) versus TD ($218,886). Estimated mean treatment costs for patients receiving VD induction in IFM 2005-01 ($201,793) and VTD induction in GIMEMA MMY-3006 ($200,093) were both lower than those for patients receiving TD induction in the MAG phase 3 trial ($239,851).
Conclusions: In summary, the model showed that total costs were lower for patients receiving bortezomib-based induction compared with TD induction in both the GIMEMA MMY-3006 and MAG trials. These health economic analyses also suggest that bortezomib-based induction results in lower mean per-patient treatment costs when compared with VAD or TD induction, primarily due to better response post-first ASCT.
Table: Cost Summaries of ASCT Trials
Induction costs VD (IFM) VTD (GIMEMA) TD (MAG) Drugs $15,940 $24,273 $16,596 Medical care $4,147 $3,578 $1,019 Adverse events $2,948 $1000 $5,610 Total induction costs (per patient) $23,035 $28,852 $23,225 Transplant costs 1st ASCT $139,220 $139,220 $139,220 2nd ASCT $39,538 $32,021 $77,406 Total transplant costs (per patient) $178,758 $171,241 $216,626 TOTAL costs $201,793 $200,093 $239,851
Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial