Phase I Study of 30-Minute Infusion of Carfilzomib As Single Agent or in Combination With Low-Dose Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

Abstract

Carfilzomib administered as a 30-minute IV infusion at 56 mg/m(2) (as single agent or with low-dose dexamethasone) was generally well tolerated and highly active in patients with relapsed and/or refractory MM. These data have provided the basis for the phase III randomized, multicenter trial ENDEAVOR.

Phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma

“…The toxicity profile for carfilzomib has been well established at the currently FDA-approved dose of 20 mg/27 mg 8,9 and is still being defined, but thus far is not significantly different, for doses up to 20 mg/56 mg. [23][24][25] Toxicities attributed to panobinostat in this trial are similar to those reported in other studies with this drug. 13,16,26,27 In particular there are two ongoing studies of carfilzomib/panobinostat combinations looking at alternative schedules of panobinostat compared to that used in this study.…”

Clinical activity of carfilzomib correlates with inhibition of multiple proteasome subunits: application of a novel pharmacodynamic assay

“…Carfilzomib has demonstrated anti‐tumour activity in patients with MM at doses ranging from 15 to 56 mg/m 2 (Siegel et al , 2012; Vij et al , 2012a,b; Badros et al , 2013; Papadopoulos et al , 2013, 2015). In phase I and II trials, only the LLVY‐AMC assay was used in a limited number of patient samples to measure CT‐L activity alone (O'Connor et al , 2009; Badros et al , 2013; Niesvizky et al , 2013; Papadopoulos et al , 2013).…”

Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

“…This has been shown to be well tolerated by reducing the incidence of infusion-related reactions. 48,49 In conclusion, the current analysis of CV events across carfilzomib clinical trials conducted to date indicates that, although cardiac AEs are numerically higher among carfilzomib-treated patients, the relative risk remains relatively low and rarely leads to dose reductions or treatment discontinuation. Moreover, the consequences are generally manageable, with no higher risk for fatal outcomes.…”