Analysis of the efficacy and safety of carfilzomib and its combination in multiple myeloma

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, Pub Med 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%（I^2 = 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 was79%（I^2 = 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.

A novel drug of elotuzumab for treatment of refractory/relapsed multiple myeloma: a meta-analysis of eight trials

Elotuzumab was approved by the US FDA in 2015 as a new drug for the treatment of multiple myeloma（MM）, and it became a new choice for MM patients. The drug is the first immunostimulatory drug to treat MM and used to treat recurrent/refractory multiple myeloma（R/RMM） in combination with lenalidomide and dexamethasone. Therefore, we collected the reports from existing clinical trials to analyze the efficacy of the drug in clinical applications to better evaluate the effects of the drug on R/RMM. The search strategy used ＂elotuzumab＂ and ＂multiple myeloma＂ as keywords to search from the database of Cochrane, Embase, Pub Med and Medline. The heterogeneity among the studies was assessed using the Cochrane χ~2 test, and its extent was evaluated using I^2 statistics. A P value of less than 0.05 was considered as statistically significant. All meta-analyses were conducted with R Software 3.3.2. We identified eight prospective studies consisting of 608 MM patients. The meta-analysis showed that the overall response rate（ORR） was 63%, 162 patients（26.6%） achieved a very good partial response rate（VGPR）, and 34 patients（5.59%） achieved complete response rate（CR）. The most common adverse effects of the drug included anemia, lymphopenia, thrombocytopenia, neutropenia and fatigue. Therefore, elotuzumab combination regimens offered clinical benefits to R/RMM patients, and such a combination therapy was a suitable option for continuous treatment for R/RMM patients.