Carfilzomib: A Payer’s Perspective

Web Exclusives

The recent FDA approval of single-agent carfilzomib (Kyprolis) adds to the armamentarium of agents for the treatment of relapsed and refractory multiple myeloma. Carfilzomib was approved based on an open-label, single-arm study of single-agent carfilzomib after the failure of at least 2 previous therapies. Within the inclusion criteria, the subjects were required to have failed bortezomib. Although bortezomib and carfilz­omib are both proteasome inhibitors, carfilzomib selectively and irreversibly binds to its target, which results in sustained proteasome inhibition that is absent of off-target effects relative to bortezomib.1,2

Despite the fact that 80% of subjects were refractory to or intolerant of bortezomib and lenalidomide, the overall response rate (ORR) was 23.7%, the mean duration of response was 7.8 months, and the median overall survival was 15.6 months.3 Subjects in this study were heavily pretreated, had a median of 5 prior lines of therapy, and were refractory to their most recent therapy.

While carfilzomib has demonstrated an ORR in a subset of patients, clinical benefit such as improvement in survival or symptoms has not been verified.4 Going forward, carfilzomib has an opportunity to demonstrate comparative outcomes in a variety of settings, which would help define its value in multiple myeloma. Value is often explained as quality relative to cost, which is often determined through comparative efficacy research. Without comparative efficacy, value (eg, improvement in quality of life, efficacy and safety, unmet need, and overall reduction in burden on healthcare) from a payer perspective is difficult to define at this juncture, but it is an exciting time with this therapy’s approval and its ongoing clinical trials. Within later line therapy, the most appropriate therapy choice is difficult to define, as providers and patients may choose to rechallenge a previous therapy as monotherapy. Doublet or triplet therapy may also be used in the relapsed and refractory setting. At this point, bortezomib with and without liposomal doxorubicin, and lenalidomide and dexamethasone have a Category 1 level of recommendation by the National Comprehensive Cancer Network for salvage therapy, while carfilzomib has received a Category 2A recommendation along with several other regimens.5 Carfilzomib is currently being studied in the ASPIRE trial in the salvage setting, in the FOCUS trial as a single agent in relapsed and refractory patients, as well as in the ENDEAVOR trial evaluating the combination of carfilzomib and low-dose dexamethasone versus the combination of bortezomib and low-dose dexamethasone. Eventually, as data from frontline therapy6,7 become available for carfilzomib, the potential for significant advances in the myeloma landscape could develop.

Payer coverage decisions for carfilzomib need to be made based on available evidence. With carfilzomib being granted accelerated approval by the FDA, along with the expense of novel therapies for the treatment of multiple myeloma, many payers will likely restrict coverage of carfilzomib to the salvage setting as a single agent based on the approved label and best available evidence. As myeloma continues to be a condition without a current cure, there remains a substantial opportunity for therapy advancement and differentiation of timely and appropriate medications and therapy combinations. Latest available evidence will continue to be used for coverage decisions including the role of carfilzomib, and as more data are released in the future, they will allow us to explore coverage in additional patient populations. It is an interesting time for payer decision, with new treatment options available and further trials ongoing, all of which should provide additional benefit for multiple myeloma patients.


  1. Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007;67:6383-6391.
  2. Groll M, Kim KB, Kairies N, et al. Crystal structure of epoxomicin:20S proteasome reveals a molecular basis for selectivity of α′,β′-epoxyketone proteasome inhibitors. J Am Chem Soc. 2000;122:1237-1238.
  3. Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120:2817-2825.
  4. Kyprolis [prescribing information]. South San Francisco, CA: Onyx Pharmaceuticals, Inc; 2012.
  5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Multiple Myeloma. Version 1.2013. Accessed November 16, 2012.
  6. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012;120:1801-1809.
  7. Landgren O, Korde N. Treating myeloma: the future is already here! Blood. 2012;120:1754-1756.


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Last modified: July 22, 2021