Practical Aspects of the Use of Carfilzomib in Multiple Myeloma

Carfilzomib (Kyprolis®, Amgen), a second-generation proteasome inhibitor, is capable of covalent bonding and irreversible inhibition of the 20S proteasome chymotrypsin-like activity. In 2016 this drug was approved in Russia for monotherapy of relapsed refractory multiple myeloma (MM) and in combinat...

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Main Authors: SV Semochkin, GN Salogub, SS Bessmeltsev, KD Kaplanov
Format: Article
Language:Russian
Published: Practical Medicine Publishing House 2018-12-01
Series:Клиническая онкогематология
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Online Access:http://bloodjournal.ru/wp-content/uploads/2018/12/3-1.pdf
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author SV Semochkin
GN Salogub
SS Bessmeltsev
KD Kaplanov
author_facet SV Semochkin
GN Salogub
SS Bessmeltsev
KD Kaplanov
author_sort SV Semochkin
collection DOAJ
description Carfilzomib (Kyprolis®, Amgen), a second-generation proteasome inhibitor, is capable of covalent bonding and irreversible inhibition of the 20S proteasome chymotrypsin-like activity. In 2016 this drug was approved in Russia for monotherapy of relapsed refractory multiple myeloma (MM) and in combination with lenalidomide and dexamethasone (KRd) or only with dexamethasone (Kd) for treatment of patients with relapsed MM after at least one line of prior therapy. The present review outlines mechanism, clinical efficacy, and adverse effects of carfilzomib according to the data of a phase II (monotherapy) trial and two key randomized phase III (carfilzomib combined with other drugs) trials. The ASPIRE trial demonstrated that adding carfilzomib to the combination of lenalidomide and dexamethasone (KRd) significantly improves progression-free survival (PFS) compared with the Rd original regimen (median 26.3 vs. 17.6 months; hazard ratio [HR] 0.69; p = 0.0001). Median overall survival (OS) was 48.3 months (95% confidence interval [95% CI] 42.4–52.8 months) for KRd vs. 40.4 months (95% CI 33.6–44.4 months) for Rd (HR 0.79; p = 0.0045). The ENDEAVOR trial showed that as compared with combination of bortezomib and dexamethasone (Vd) the carfilzomib + dexamethasone (Kd) regimen significantly improves PFS (median 18.7 vs. 9.4 months; HR 0.53; p < 0.0001) and OS (47.6 vs. 40.0 months; HR 0.79; p = 0.010) as well. The present review also discusses how carfilzomib is to be used in special patient groups (with renal failure and high cytogenetic risk).
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spelling doaj-art-4223f6d4c83a4be9a4f4e7f879b1d8f62025-08-20T01:56:52ZrusPractical Medicine Publishing HouseКлиническая онкогематология1997-69332500-21392018-12-01121213110.21320/2500-2139-2019-12-1-21-31Practical Aspects of the Use of Carfilzomib in Multiple MyelomaSV Semochkin0GN Salogub1SS Bessmeltsev2KD Kaplanov3NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997; Municipal Clinical Hospital No. 52, 3 Pekhotnaya str., Moscow, Russian Federation, 123182VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138Carfilzomib (Kyprolis®, Amgen), a second-generation proteasome inhibitor, is capable of covalent bonding and irreversible inhibition of the 20S proteasome chymotrypsin-like activity. In 2016 this drug was approved in Russia for monotherapy of relapsed refractory multiple myeloma (MM) and in combination with lenalidomide and dexamethasone (KRd) or only with dexamethasone (Kd) for treatment of patients with relapsed MM after at least one line of prior therapy. The present review outlines mechanism, clinical efficacy, and adverse effects of carfilzomib according to the data of a phase II (monotherapy) trial and two key randomized phase III (carfilzomib combined with other drugs) trials. The ASPIRE trial demonstrated that adding carfilzomib to the combination of lenalidomide and dexamethasone (KRd) significantly improves progression-free survival (PFS) compared with the Rd original regimen (median 26.3 vs. 17.6 months; hazard ratio [HR] 0.69; p = 0.0001). Median overall survival (OS) was 48.3 months (95% confidence interval [95% CI] 42.4–52.8 months) for KRd vs. 40.4 months (95% CI 33.6–44.4 months) for Rd (HR 0.79; p = 0.0045). The ENDEAVOR trial showed that as compared with combination of bortezomib and dexamethasone (Vd) the carfilzomib + dexamethasone (Kd) regimen significantly improves PFS (median 18.7 vs. 9.4 months; HR 0.53; p < 0.0001) and OS (47.6 vs. 40.0 months; HR 0.79; p = 0.010) as well. The present review also discusses how carfilzomib is to be used in special patient groups (with renal failure and high cytogenetic risk).http://bloodjournal.ru/wp-content/uploads/2018/12/3-1.pdfproteasome inhibitorlenalidomidebortezomibmultiple myelomarenal failurecarfilzomibcytogenetic risk
spellingShingle SV Semochkin
GN Salogub
SS Bessmeltsev
KD Kaplanov
Practical Aspects of the Use of Carfilzomib in Multiple Myeloma
Клиническая онкогематология
proteasome inhibitor
lenalidomide
bortezomib
multiple myeloma
renal failure
carfilzomib
cytogenetic risk
title Practical Aspects of the Use of Carfilzomib in Multiple Myeloma
title_full Practical Aspects of the Use of Carfilzomib in Multiple Myeloma
title_fullStr Practical Aspects of the Use of Carfilzomib in Multiple Myeloma
title_full_unstemmed Practical Aspects of the Use of Carfilzomib in Multiple Myeloma
title_short Practical Aspects of the Use of Carfilzomib in Multiple Myeloma
title_sort practical aspects of the use of carfilzomib in multiple myeloma
topic proteasome inhibitor
lenalidomide
bortezomib
multiple myeloma
renal failure
carfilzomib
cytogenetic risk
url http://bloodjournal.ru/wp-content/uploads/2018/12/3-1.pdf
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