A Budget Impact Model Comparing Resource Utilization of Four Approved Therapies for Multiple Myeloma (MM) in the US.
Authors: Fullerton D.S. Pete , Trautman Holly , Huang Hui , Veljkovic Jelena , Esseltine Dixie-Lee , Marantz Jing 
Published: October 2019

Abstract
Background: MM treatment has changed substantially in the past 5 years as a result of the FDA approval of single agent bortezomib (VELCADE®, Vel), the combinations of thalidomide (Thalomid®, Thal) plus dexamethasone (Dex), lenalidomide (Revlimid®, Rev) plus Dex, and most recently Vel with pegylated liposomal doxorubicin (DOXIL®, Dox). The aim of this budget impact model was to evaluate the direct resource utilization of these 4 therapies, including drug cost, medical cost and cost of management of adverse events (AE).
Methods: A managed care payer perspective was used. Drug costs were calculated based on AWP - 15% with 10% (Thal/Dex, Rev/Dex) or 20% (Vel, Vel/Dox) patient coinsurance. Cost of therapy and costs of treating each AE were obtained from standard sources such as the Red Book or from peer-reviewed publications and/or meeting presentations. Incidence of AE (all ≥5% grade 3/4 AE or AE that require significant resource utilization) and assumptions for supportive care/prophylaxis were obtained from the full Prescribing Information (PI) for each of the 4 approved MM therapies. For key AE with no information available in the PI, data were obtained from peer-reviewed publications. Specifically, the rates of febrile neutropenia and DVT/PE for Vel/Dox were obtained from the pivotal ph3 trial (Orlowski et al, JCO 2007), while the rates of grade 3/4 dyspnea, pneumonia/grade 3/4 infections were inferred from Orlowski et al, ASH 2006; the rate of febrile neutropenia for Rev/Dex was obtained from the pivotal ph3 study (Dimopoulos et al, EHA 2006). Duration of therapy (DOT) for each regimen was based on the published median DOT of the respective pivotal ph3 study: 6 cycles for Vel (Richardson, NEJM 2005) and Vel/Dox (Orlowski, JCO 2007), and 11 cycles for Rev/Dex (Stadtmauer, ASCO 2006). DOT for Thal/Dex (9 cycles) was based on the average DOT from 2 ph2 studies (Palumbo, Haematologica 2001; Terpos, Leukemia 2005) as it better reflects actual use. Medical costs included evaluation and management, chemotherapy administration, hydration, laboratory tests and prophylaxis. This analysis did not account for differences in patient population or in efficacy; efficacy could not be compared due to incomplete/inconsistent reporting of outcomes data in the PIs for the 4 regimens.
Results: Total costs for these 4 regimens were substantially different, primarily driven by direct drug costs (Table). Based on emerging clinical data, prophylaxis for herpes zoster (Vel, Vel/Dox) and DVT/PE (Rev/Dex, Thal/Dex) are recommended. Thus we performed an additional analysis assuming appropriate prophylaxis based on published literature. The total costs +/− prophylaxis did not differ substantially as increased medical costs offset decreased AE management costs.
Conclusions: This analysis showed a substantial difference in resource utilization for the 4 US approved MM regimens with Vel being the lowest and Rev/Dex the highest. A complete cost-effectiveness model is warranted as more outcomes data become available.
Vel Vel/Dox Rev/Dex Thal/Dex *with prophylaxis;data not available w/o prophylaxis Drug Costs $22,734 $34,794 $64,806 $37,281 Medical Costs $5,886 $7,041* $1,623 $1,397 AE Costs $5,209 $6,094* $5,243 $7,910 TOTAL (per patient) $33,829 $47,929* $71,672 $46,588 TOTAL w/ prophylaxis (per patient) $33,966 $47,929 $72,822 $47,002 type of prophylaxis herpes zoster DVT/PE