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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Practical Medicine Publishing House
2018-12-01
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| 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). |
| format | Article |
| id | doaj-art-4223f6d4c83a4be9a4f4e7f879b1d8f6 |
| institution | OA Journals |
| issn | 1997-6933 2500-2139 |
| language | Russian |
| publishDate | 2018-12-01 |
| publisher | Practical Medicine Publishing House |
| record_format | Article |
| series | Клиническая онкогематология |
| 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 |
| work_keys_str_mv | AT svsemochkin practicalaspectsoftheuseofcarfilzomibinmultiplemyeloma AT gnsalogub practicalaspectsoftheuseofcarfilzomibinmultiplemyeloma AT ssbessmeltsev practicalaspectsoftheuseofcarfilzomibinmultiplemyeloma AT kdkaplanov practicalaspectsoftheuseofcarfilzomibinmultiplemyeloma |