Abstract
We conducted a systematic review to determine the appropriate use of bortezomib alone or in combination with other agents in patients with multiple myeloma (mm). We searched medline, embase, the Cochrane Library, conference proceedings, and the reference lists of included studies. We analyzed randomized controlled trials and systematic reviews if they involved adult mm patients treated with bortezomib and if they reported on survival, disease control, response, quality of life, or adverse effects. Twenty-six unique studies met the inclusion criteria. For patients with previously untreated mm and for candidates for transplantation, we found a statistically significant benefit in time to progression [hazard ratio (hr): 0.48, p < 0.001; and hr: 0.63, p = 0.006, respectively] and a better response with a bortezomib than with a non-bortezomib regimen (p < 0.001). Progression-free survival was longer with bortezomib and thalidomide than with thalidomide alone (p = 0.01). In non-candidates for transplantation, a significant benefit in overall survival was observed with a bortezomib regimen (hr compared with a non-bortezomib regimen: 0.61; p = 0.008), and in transplantation candidates receiving bortezomib, the response rate was improved after induction (p = 0.004) and after a first transplant (p = 0.016). In relapsed or refractory mm, overall survival (p = 0.03), time to progression (hr: 1.82; p = 0.000004), and progression-free survival (hr: 1.69; p = 0.000026) were significantly improved with bortezomib and pegylated liposomal doxorubicin (compared with bortezomib alone), and bortezomib monotherapy was better than dexamethasone alone (hr: 0.77; p = 0.027). Bortezomib combined with thalidomide and dexamethasone was better than either bortezomib monotherapy or thalidomide with dexamethasone (p < 0.001). In previously untreated or in relapsed or refractory mm patients, bortezomib-based therapy has improved disease control and, in some patients, overall survival.
Highlights
Bortezomib (Velcade: Millennium Pharmaceuticals, Cambridge, MA, U.S.A.), a first-in-class proteasome inhibitor, has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma
Given that new data have recently become available, the Hematology Disease Site Group at Cancer Care Ontario, in collaboration with the Program in Evidence-Based Care, conducted a systematic review to determine the appropriate use of bortezomib in patients with mm
In patients with previously untreated mm who are not candidates for asct, bortezomib combined with melphalan and prednisone is the preferred firstline therapy
Summary
Bortezomib (Velcade: Millennium Pharmaceuticals, Cambridge, MA, U.S.A.), a first-in-class proteasome inhibitor, has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma (mm). Bortezomib works in the ubiquitin–proteasome pathway of cellular protein homeostasis by blocking the action of the 26S proteasome, a multicatalytic enzyme that degrades abnormal or misfolded proteins targeted for destruction, those involved in cell cycling and gene transcription. Because those proteins are more abundant during the processes of carcinogenesis, they are key in cancer survival; proteasome inhibition in cancer cells leads to cell apoptosis and is, a target for therapy[1]. This review constitutes the evidentiary basis of an updated Cancer Care Ontario guideline on bortezomib for mm and lymphoma (available at https://www.cancercare. on.ca/common/pages/UserFile.aspx?fileId=34323)
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