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Author: Admin | 2025-04-28
Dexamethasone, or a combination of both. Proteasome inhibitors Bortezomib. Bortezomib monotherapy is effective in patients with relapsed MM, as was demonstrated in pivotal studies.28 It can safely and effectively be administered to patients with renal impairment. Its main toxicities include peripheral neuropathy, which may preclude further treatment, gastrointestinal symptoms, and transient thrombocytopenia. Bortezomib, in comparison with dexamethasone, improved outcomes in patients with RRMM in the APEX trial.29 Patients treated with bortezomib have higher ORRs (38% vs 18%; CR 6% vs P P P = .003) than did those treated with dexamethasone. The drug is now routinely administered subcutaneously, which improves tolerance while keeping efficacy.30 It is now routinely used in a weekly schedule in elderly patients.31 Retreatment with bortezomib has clinical value if the patients were responsive before and if the response lasted more than 6 months.32 Bortezomib is effective in combination with other agents such as anthracyclins. Bortezomib in combination with dexamethasone and pegylated liposomal doxorubicin showed improved TTP (9.3 vs 6.5 months) and OS (76% vs 65%) and good tolerability. Bortezomib can be combined with weekly oral cyclophosphamide (300-500 mg/m2) and dexamethasone or prednisone.33 Bortezomib is also effective as part of triple or quadruple drug salvage regimens (ORR 56% to 88%; CR 6% to 46%; VGPR or better, 34% to 55%), and favorable response rates have been reported of CTD (VCTD); bortezomib plus melphalan and prednisone; and bortezomib with doxorubicin, dexamethasone, and lenalidomide. Bortezomib may enhance the effects of the IMiDs thalidomide and lenalidomide. Bortezomib plus thalidomide/dexamethasone (VTD) was more effective than was thalidomide/dexamethasone for TTP (19.5 vs 13.8 months), CR/near CR (45% vs 25%), and duration of response (17.2 vs 13.4 months) in patients who relapsed after ASCT. Currently, one of the most effective and widely used regimens is bortezomib plus lenalidomide and dexamethasone. In a phase 1 trial in RRMM, ORR was 61% and OS of 37 months.34 Grades 3 and 4 toxicities were myelosuppression, whereas only grades 1 and 2 polyneuropathy was observed. In conclusion, bortezomib combined with dexamethasone is an effective treatment of RRMM. Its efficacy is increased when combined with thalidomide, lenalidomide, cyclophosphamide, or an anthracyclin. Patients should be carefully monitored for peripheral neuropathy, in case the dose and schedule should be reduced. Two next-generation PIs became available in 2016, that is, intravenous carfilzomib and oral ixazomib. Carfilzomib irreversibly binds to the proteasome subunit and has been dosed at levels ranging from 27 mg/m2 to 70 mg/m2 weekly. Its safety profile is dominated by cardiovascular toxicity, including hypertension and congestive heart failure. Carfilzomib has been compared as single agent with dexamethasone (FOCUS trial) without a clear PFS benefit. This also suggests that carfilzomib must be combined with other agents. Carfilzomib plus dexamethasone was
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