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Analysis of the efficacy and safety of carfilzomib and its combination in multiple myeloma
Authors:Lin Zhang  Xiaoxuan Jin  Shuting Huang  Wenyu Xu  Jiewei Ding
Abstract:Carfilzomib has become a new choice for patients with multiple myeloma (MM). However, the use of carfilzomib single-agent or in combination with other agents in MM patients is not explicitly clarified in clinical practice. Therefore, we analyzed the effects of carfilzomib and its safety and effectiveness using available clinical trial reports in order to find out the best therapy of carfilzomib. We searched MEDLINE, Embase, PubMed and Cochrane databases as well as Chinese databases of carfilzomib trials (Jan. 2012 to Sep. 2016) for the MM treatment. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as the overall response rate (ORR) and performed by R software. A fixed-effects model or random-effects model was applied based on the heterogeneity among studies. Based on our research standard, we identified 17 prospective studies enrolling 1960 patients. A total of 594 MM patients were enrolled in carfilzomib single-agent clinical trials, and the ORR was 32% (I2 = 84.9%, P<0.0001). A total of 1366 MM patients were enrolled in clinical trials of 10 groups of carfilzomib combination regimens, 1081 patients had a therapeutic effect, and the ORR was 79% (I2 = 91.0%, P<0.0001). The most frequent adverse events were fever, nausea, vomiting and other non-hematologic events. Carfilzomib was better tolerated than bortezomib, with a lower incidence of peripheral neuropathy and better therapeutic effects compared with other drugs. In this analysis, the highest ORR was achieved from combination of carfilzomib, lenalidomide and dexamethasone, which had a lower incidence of adverse events and a greater ORR compared with carfilzomib single-agent. Therefore, the combination of carfilzomib, lenalidomide and dexamethasone could be a good therapeutic agent with strong clinical effect. However, this conclusion needs to be validated in future study.
Keywords:Carfilzomib  Multiple myeloma  Meta-analysis  
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