Bortezomib in Multiple Myeloma: Systematic Review and Clinical Considerations

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

Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption

“…A wide variety of agents, including inhibitors of protein kinases, protein phosphatases, proteasomes, ubiquitination, acetylation, methylation, and the DNA-binding steps of NF-kB signaling pathway, have been identified as potential NF-kB-targeting agents (36). Some of these are in clinical treatment or trials for certain cancer types (38,39). Bortezomib, the most-studied proteasome inhibitor, has been approved for treating multiple myeloma and mantle cell lymphoma (40) and is also in clinical trials for many liquid and solid tumors (33).…”

Identification of Thiostrepton as a Novel Inhibitor for Psoriasis-like Inflammation Induced by TLR7–9

“…Additionally, treatment applications of this small-molecular mass compound for autoimmune disorders are in preclinical investigation with animal models. Nevertheless, the adverse effect of neurotoxicity limits the therapeutic applications of bortezomib (30)(31)(32)57). To explore the applications of novel TLR7-9 inhibitors with respect to autoimmune diseases, in this study we designed a strategy to screen the CMap database for chemical compounds with similar functions as bortezomib.…”

“…This drug is also an NF-kB inhibitor, and its inhibitory effects on autoimmune disorders such as psoriasis, RA, and SLE have been shown in animal models (30)(31)(32). Although the functional mechanism has not yet been fully elucidated, bortezomib has been shown to inhibit TLR9 activation by suppressing trafficking of this TLR to the endolysosomes and reducing the inflammation induced in lupus and psoriasis (33,34).…”

Anti-tumor activity of the proteasome inhibitor BSc2118 against human multiple myeloma

“…It significantly improves the prognosis and prolongs overall survival of MM patients [31,32]. Despite the high initial response rate to bortezomib, relapse remains inevitable.…”