Intravenous carfilzomib is a peptide epoxyketone, next-generation proteasome inhibitor, which has been granted accelerated approval in the US for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent (thalidomide or lenalidomide), and have demonstrated disease progression on or within 60 days of completion of the last therapy.
Carfilzomib displays high selectivity for and irreversibly inhibits the chymotrypsin-like catalytic activity of the 20S proteasome core particle, which results in cell growth arrest and apoptosis.
In the pivotal, phase II, noncomparative trial in heavily pre-treated patients (n = 266) with relapsed and refractory multiple myeloma, intravenous carfilzomib administered in 28-day cycles for up to 12 cycles produced an overall response rate of 23.7% in the response-evaluable population. The median duration of response was 7.8 months, the median progression-free survival was 3.7 months and the median overall survival was 15.6 months.
Carfilzomib had an acceptable tolerability profile in patients with relapsed, or relapsed and refractory, multiple myeloma. There was a low incidence of grade 3 or higher peripheral neuropathy.
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Acknowledgements and Disclosures
The manuscript was reviewed by A.Z. Badros, Bone Marrow Transplant Program, Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA; J. Richter, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.
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McCormack, P.L. Carfilzomib. Drugs 72, 2023–2032 (2012). https://doi.org/10.2165/11209010-000000000-00000
- Multiple Myeloma
- Overall Response Rate