Treatment outcomes, health-care resource utilization and costs of bortezomib and dexamethasone, with cyclophosphamide or lenalidomide, in newly diagnosed multiple myeloma

Abstract

The introduction of proteasome inhibitors and immunomodulatory drugs has led to significant survival improvements in multiple myeloma (MM). 1,2 Two of the most commonly used regimens for initial MM therapy are bortezomib/dexamethasone plus either cyclophosphamide (VCD) or lenalidomide (VRD). 3 Although not compared head-to-head, phase-2 trials results support the use of either regimen for newly diagnosed MM (NDMM). 4-7 While more efficacious than previous classes, these drugs are associated with substantial cost. [8][9][10] In an era focusing on value of care and efficient resource allocation, use of VCD may lower costs by employing only one novel drug, 'reserving' lenalidomide for subsequent line(s) of therapy. This is particularly relevant for MM where no curative treatments exist, and all available therapies may be used along the care continuum. A paucity of comparative effectiveness research on VCD and VRD as initial therapies for MM exists, thus we designed this retrospective, non-interventional, observational cohort study to compare clinical outcomes, healthcare resource utilization (HRU) and total healthcare costs of VCD and VRD as initial MM treatment in the US clinical setting.Medical charts of a random sample of 176 NDMM patients who initiated VCD or VRD at Mayo Clinic, Rochester, or within the US Oncology Network in January 2008-August 2013 were studied. Patients with ≥2 clinic visits and ≥6 months' follow-up from VCD/VRD initiation were included; those treated in clinical trials were excluded. Study was conducted per the Helsinki Declaration, with Institutional Review Board approvals.Best overall response after 4 cycles and end-of-treatment, progression-free (PFS) and overall (OS) survival (overall, 1-and 2-year), adverse events (AEs), HRU, and total costs (US payer's perspective) were evaluated. With a sample size of N=182, there would be ≥80% power to detect a minimum acceptable best response rate of 60% (ie. 0.70 relative response rate), at one-sided =0.05.Comparisons between VCD/VRD employed adjusted logistic regressions for response; chi-square tests for AEs; and Kaplan-Meier methodology and log-rank tests for overall PFS and OS. Adjusted analyses using Cox proportional models compared 1-and 2-year PFS and OS between cohorts. Adjusted Poisson regression models compared incidence rates of HRU between cohorts.Healthcare costs were compared using unadjusted and adjusted cost difference.Adjusted models controlled for treatment site/network, insurance type, ISS stage III disease, stem cell transplant (SCT), renal failure, cardiac disease, diabetes mellitus and bone fractures.Of 176 patients, 101 (57%) received VCD and 75 (43%) VRD in frontline.Baseline characteristics, including comorbidities, were generally similar between cohorts, except for a higher proportion of African Americans in the VRD cohort (9% versus VCD 2%; P=0.03). A higher proportion of patients with renal failure was seen in the VCD cohort (38% versus VRD 19%; P=0.006), likely reflecting 6 Kumar VCD vs VRD outcomes NDMM_Leukemia_23Jun...

Myeloma today: Disease definitions and treatment advances

“…VCD (also referred to as CyBorD) is an alternative; it is less expensive than either VTD or VRD. 62,66 However, response rates are lower with VCD compared with VTD. Bortezomib-containing regimens also appear to overcome the poor prognosis associated with the t4;14 translocation, and certain other cytogenetic abnormalities.…”

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma

“…A direct comparison of VCd and VRd or ICd and IRd are not available from a clinical trial setting. In a retrospective study of the two regimens, the efficacy appeared to be comparable between the VCd and VRd regimens, but no similar data exist as of now for ICd and IRd 33 . As with the bortezomib and lenalidomide combinations, longer duration of therapy translated into a deeper response and the lack of peripheral neuropathy can potentially allow for longer therapy.…”

Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial

“…Indeed, a recent retrospective comparison of VCD and VRD induction reported comparable outcomes in terms of response, PFS and OS (Kumar et al , ), indicating that the substantially increased costs associated with combining two novel agents in the VRD regimen may not be justified in terms of outcome benefit versus the VCD regimen. Further analysis showed that, in terms of cost efficacy and health resource utilisation, VCD is preferable to VRD for induction (Kumar et al , ).…”