An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib

Ravi Vij, David S. Siegel, Sundar Jagannath, Andrzej J. Jakubowiak, Alexander Keith Stewart, Kevin Mcdonagh, Nizar Bahlis, Andrew Belch, Lori A. Kunkel, Sandra Wear, Alvin F. Wong, Robert Z. Orlowski, Michael Wang

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Carfilzomib is a next-generation proteasome inhibitor that selectively and irreversibly binds to its target. In clinical studies, carfilzomib has shown efficacy in patients with relapsed and/or refractory multiple myeloma (MM) and has demonstrated a tolerable safety profile. In this phase 2, open-label, multicentre clinical trial, 35 patients with relapsed and/or refractory MM following 1-3 prior therapies, including at least one bortezomib-based regimen, received carfilzomib 20 mg/m2 in a twice-weekly, consecutive-day dosing schedule for ≤12 monthly cycles. The best overall response rate (ORR) was 17·1% and the clinical benefit response rate (ORR + minimal response) was 31·4%. The median duration of response was >10·6 months and the median time to progression was 4·6 months. The most common adverse events were fatigue (62·9%), nausea (60·0%), and vomiting (42·9%). No exacerbation of baseline peripheral neuropathy was observed. Single-agent carfilzomib was generally well tolerated for up to 12 treatment cycles and showed activity in patients with relapsed and/or refractory MM who had received prior treatment with bortezomib. These data, combined with an acceptable toxicity profile, support the potential use of carfilzomib in patients with relapsed and/or refractory MM and warrant continued investigation of carfilzomib as single agent or in combination with other agents.

Original languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalBritish Journal of Haematology
Volume158
Issue number6
DOIs
StatePublished - Sep 2012

Fingerprint

Multiple Myeloma
Activity Cycles
Proteasome Inhibitors
Peripheral Nervous System Diseases
Nausea
Multicenter Studies
Vomiting
Fatigue
Bortezomib
carfilzomib
Appointments and Schedules
Therapeutics
Clinical Trials
Safety

Keywords

  • Multiple myeloma
  • Phase 2
  • Proteasome inhibitor
  • Refractory
  • Relapsed

ASJC Scopus subject areas

  • Hematology

Cite this

An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. / Vij, Ravi; Siegel, David S.; Jagannath, Sundar; Jakubowiak, Andrzej J.; Stewart, Alexander Keith; Mcdonagh, Kevin; Bahlis, Nizar; Belch, Andrew; Kunkel, Lori A.; Wear, Sandra; Wong, Alvin F.; Orlowski, Robert Z.; Wang, Michael.

In: British Journal of Haematology, Vol. 158, No. 6, 09.2012, p. 739-748.

Research output: Contribution to journalArticle

Vij, R, Siegel, DS, Jagannath, S, Jakubowiak, AJ, Stewart, AK, Mcdonagh, K, Bahlis, N, Belch, A, Kunkel, LA, Wear, S, Wong, AF, Orlowski, RZ & Wang, M 2012, 'An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib', British Journal of Haematology, vol. 158, no. 6, pp. 739-748. https://doi.org/10.1111/j.1365-2141.2012.09232.x
Vij, Ravi ; Siegel, David S. ; Jagannath, Sundar ; Jakubowiak, Andrzej J. ; Stewart, Alexander Keith ; Mcdonagh, Kevin ; Bahlis, Nizar ; Belch, Andrew ; Kunkel, Lori A. ; Wear, Sandra ; Wong, Alvin F. ; Orlowski, Robert Z. ; Wang, Michael. / An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. In: British Journal of Haematology. 2012 ; Vol. 158, No. 6. pp. 739-748.
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abstract = "Carfilzomib is a next-generation proteasome inhibitor that selectively and irreversibly binds to its target. In clinical studies, carfilzomib has shown efficacy in patients with relapsed and/or refractory multiple myeloma (MM) and has demonstrated a tolerable safety profile. In this phase 2, open-label, multicentre clinical trial, 35 patients with relapsed and/or refractory MM following 1-3 prior therapies, including at least one bortezomib-based regimen, received carfilzomib 20 mg/m2 in a twice-weekly, consecutive-day dosing schedule for ≤12 monthly cycles. The best overall response rate (ORR) was 17·1{\%} and the clinical benefit response rate (ORR + minimal response) was 31·4{\%}. The median duration of response was >10·6 months and the median time to progression was 4·6 months. The most common adverse events were fatigue (62·9{\%}), nausea (60·0{\%}), and vomiting (42·9{\%}). No exacerbation of baseline peripheral neuropathy was observed. Single-agent carfilzomib was generally well tolerated for up to 12 treatment cycles and showed activity in patients with relapsed and/or refractory MM who had received prior treatment with bortezomib. These data, combined with an acceptable toxicity profile, support the potential use of carfilzomib in patients with relapsed and/or refractory MM and warrant continued investigation of carfilzomib as single agent or in combination with other agents.",
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