An open-label, single-arm, phase2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma

Ravi Vij, Michael Wang, Jonathan L. Kaufman, Sagar Lonial, Andrzej J. Jakubowiak, A. Keith Stewart, Vishal Kukreti, Sundar Jagannath, Kevin T. McDonagh, Melissa Alsina, Nizar J. Bahlis, Frederic J. Reu, Nashat Y. Gabrail, Andrew Belch, Jeffrey V. Matous, Peter Lee, Peter Rosen, Michael Sebag, David H. Vesole, Lori A. KunkelSandra M. Wear, Alvin F. Wong, Robert Z. Orlowski, David S. Siegel

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220 Scopus citations

Abstract

Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomibnaive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m2 for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m2 for cycle 1 and then 27 mg/m2 for all subsequent cycles. The primary end point was an overall response rate (≥ partial response) of 42.4% in Cohort 1 and 52.2% in Cohort 2. The clinical benefit response (overall response rate + minimal response) was 59.3% and 64.2% in Cohorts 1 and 2, respectively. Median duration of response was 13.1 months and not reached, and median time to progression was 8.3 months and not reached, respectively. The most common treatment-emergent adverse events were fatigue (62.0%) and nausea (48.8%). Single-agent carfilzomib elicited a low incidence of peripheral neuropathy - 17.1% overall (1 grade 3; no grade 4) - in these pretreated bortezomib-naive patients. The results of the present study support the use of carfilzomib in R/R MM patients. This trial is registered at www.clinicaltrials.gov as NCT00530816.

Original languageEnglish (US)
Pages (from-to)5661-5670
Number of pages10
JournalBlood
Volume119
Issue number24
DOIs
StatePublished - Jun 14 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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