No abstract

Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e.g. days 1-4, 8-11). Pooled overall PN rates were 45·5%, 63·9%, and 47·5%, respectively, with 5·3%, 11·0%, and 9·6% grade ≥3. Adjusting for potential confounders (age, gender, presence of thalidomide, bortezomib treatment duration), PN rates in patients on partnered dosing schedules appeared lower than in patients on weekly or other dosing schedules. Analyses conducted using patient-level data suggest that cumulative dexamethasone dose, a potential confounding factor, is unlikely to have influenced the analyses. Findings were similar in a separate pooled analysis excluding data from regimens incorporating thalidomide, when pooled overall PN rates were 50·1%, 63·9%, and 48·3%, respectively, with 4·2%, 11·0%, and 8·6% grade ≥3. These findings suggest that partnered dexamethasone dosing may result in less severe BiPN compared with alternative dexamethasone dosing schedules.

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...