Carfilzomib is a selective, irreversible proteasome inhibitor, initially approved in the US in 2012 as single-agent therapy for relapsed and refractory multiple myeloma. Numerous Phase II studies have evaluated carfilzomib in the relapsed and refractory as well as the newly diagnosed setting, and Phase III studies are entering their final analysis. Data continue to grow to support its use as both single-agent therapy and in combination with immunomodulatory and other novel agents. This review discusses the role of carfilzomib in the treatment of multiple myeloma. Its mechanism of action, pharmacokinetics, and role in clinical management will be reviewed.

The current study presents the case of a 63-year-old patient exhibiting refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), who was positive for the MPL W515L mutation, but negative for the JAK2 V617F mutation. Following diagnosis, the patient remained asymptomatic for over three years, however, in August 2012, the patient relapsed and was administered with supportive treatment in the form of subcutaneous darbepoetin α at a dose of 300 μg/week, which resulted in an increased hemoglobin concentration, allowing the patient to remain transfusion-independent. The MPL W515L mutation has been reported in two previous cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with ringed sideroblasts, however, to the best of our knowledge, the current report is the first to present a case of RARS-T with an MPL W515L mutation. A clinical trial designed to evaluate the efficacy of a targeted agent against the JAK2 V617F mutation is currently ongoing, with the aim of providing a novel therapeutic strategy for treating MDS/MPN patients. As MPL is located upstream of the JAK-STAT signaling pathway, it is a possible therapeutic target in MDS/MPN patients positive for an MPL W515L mutation, but negative for a JAK2 V617F mutation.

(4%). The median cell dose was 5.5 x 10 6 CD34+ cells/kg (range 2.86 to 12.3 x 10 6). No patient died within 100 days of transplant. The median follow up was 27 months (range 1.5 to 79.8). The median overall survival at 1 year, 3 years, and 5 years was 87%, 77%, and 77%. Relapse free survival at 1 year, 3 years, and 5 years was 78%, 68%, and 68%. In conclusion, bortezomib-based therapy followed by ASCT is well tolerated and can be performed with low TRM, resulting in durable OS and RFS.

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