Cost-Effectiveness of Once-Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) Versus Twice-Weekly Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma
Authors: Patel Kishan , Parker Terri L. , Di Mengyang , Bar Noffar , Huntington Scott F. , Giri Smith 
Published: February 2021

Introduction: The phase III BOSTON trial reported that once-weekly therapy with selinexor, bortezomib, and dexamethasone (SVd) significantly prolonged progression-free survival for patients with relapsed or refractory (R/R) multiple myeloma compared to twice-weekly treatment with bortezomib and dexamethasone alone (Vd). Although once-weekly SVd reduces the risk of disease progression as well as the cumulative exposure of patients to bortezomib and dexamethasone, selinexor is a costly drug-priced at nearly $22,000 per month-and is associated with significant toxicity. As a result, it is unclear whether SVd provides sufficient value in this clinical setting. In this study, we assess the cost-effectiveness of once-weekly SVd versus twice-weekly Vd in patients with R/R multiple myeloma.
Methods: Our cost-effectiveness analysis was based on a Markov model. Simulated patients mirrored the cohort studied in the BOSTON trial; the median age of the population was 66 years, 57% were male and all had received 1-3 prior lines of therapy. Patients entered the model with R/R myeloma and received treatment with SVd or Vd; upon disease progression, all patients subsequently received identical lines of post-progression therapy. Our base-case model (Figure 1) followed SVd/Vd progression sequentially with daratumumab, carfilzomib, and dexamethasone (DKd), pomalidomide and dexamethasone (Pd), and best supportive care. We derived transition probabilities from large randomized trials using parametric survival modeling. The utility of each health state and the costs of treatment, adverse events, and terminal care were derived from literature and Medicare fee schedules. As data evaluating the quality of life with SVd vs Vd is not yet available, we assumed identical utility values for both treatment regimens. We calculated the incremental cost effectiveness ratio (ICER) from a US payer perspective, using a lifetime horizon, an annual discount rate of 3%, and a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were conducted to evaluate uncertainty in our model.
Results: In our base-case model, SVd was associated with an improvement of 0.37 QALYs compared to Vd alone (3.43 vs 3.06 QALYs, respectively). However, the incremental lifetime cost of SVd was $177,126 ($1,013,851 vs $836,725, respectively), leading to an ICER of $479,572/QALY. The monthly cost of selinexor would need to be decreased by approximately 51%, from $21,424 to $10,415, in order for SVd to be cost-effective compared to Vd alone in R/R patients. Our model was most sensitive to the hazard ratio of SVd relative to Vd; decreasing the HR from 0.70 to 0.53 decreased the ICER to $285,251/QALY, while increasing the HR to 0.93 increased the ICER to $1,738,546/QALY. Of note, all ICERs during one-way sensitivity analysis and &gt;99% of ICERs during probabilistic sensitivity analysis remained above the willingness-to-pay threshold of $150,000 QALY. We also incorporated two scenario analyses; in the first, patients in the Vd arm received therapy with selinexor and dexamethasone (Sd) after progression from Pd, before receiving best supportive care. In this scenario, SVd was associated with an incremental cost of $112,445 ($1,013,851 vs $901,406), an incremental effectiveness of 0.24 QALYs (3.43 vs 3.19 QALYs), and an ICER of $464,557/QALY. In the second scenario analysis, we assumed that patients had received DKd prior to SVd/Vd; as a result, patients that progressed on SVd or Vd subsequently received Pd followed by best supportive care. Here, SVd was associated with an incremental cost of $222,864 ($418,526 vs $195,662), an incremental effectiveness of 0.49 QALYs (1.90 vs 1.41 QALYs), and an ICER of $456,080/QALY.
Conclusions: Use of once-weekly SVd for patients with relapsed or refractory multiple myeloma is unlikely to be cost-effective under current pricing, compared to twice-weekly Vd. The price of selinexor would need to be decreased substantially in order to reduce the ICER of SVd to widely acceptable values.

Disclosures
Huntington: DTRM: Research Funding; Pharmacyclics: Honoraria; TG Therapeutics: Research Funding; Genentech: Consultancy; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; AbbVie: Consultancy; Novartis: Consultancy. Giri:Carevive Systems: Research Funding; Carevive Systems: Honoraria; Pack Health: Research Funding.