Thrombotic microangiopathy during carfilzomib use: case series in Singapore

Carfilzomib is an irreversible proteasome inhibitor and is an effective treatment for multiple myeloma (MM).1, 2 It received US Food and Drug Administration approval based on a single-arm multicenter trial of carfilzomib monotherapy in 266 patients with relapsed MM following at least two prior lines of treatment including bortezomib and immunomodulators.1, 3 Safety analyses from four phase II carfilzomib trials (N=526) that included heavily pre-treated MM patients suggested a favorable risk-benefit profile with no specific signal of thrombotic microangiopathy (TMA) reported. However, serious adverse events of anemia, thrombocytopenia and increased serum creatinine comprised 1.3%, 1.1% and 1.3%, respectively.4 Over 350 subjects have been enrolled in randomized phase III trials in Asian countries. Herein, we report four cases of TMA related to carfilzomib use among 24 patients from 2 tertiary hospitals in Singapore (Table 1). All patients who started carfilzomib had a creatinine clearance >30 ml/min and platelet counts>50 × 109/l at the start of treatment.