Abstract
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.
Highlights
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
Platelet counts and renal function recovered to baseline 4 days after diagnosis of TMA and cessation of carfilzomib
The patient required temporary hemodialysis but not plasmapheresis. Her platelet counts recovered after 7 days and renal function normalized after 1 month
Summary
Blood Cancer Journal (2016) 6, e450; doi:10.1038/bcj.2016.62; published online 29 July 2016. Patients 1 (70/Chinese/Male) and 2 (66/Chinese/Female) had newly diagnosed MM and were treated in an institutional review board-approved investigator-initiated study (IIS) using carfilzomib in combination with cyclophosphamide and dexamethasone as frontline therapy for high-risk MM (SGHMM1, NCT02217163) Within this trial, carfilzomib is given at 20 mg/m2 in cycle (C) 1, days (D) 1 and 2 followed by 56 mg/m2 for all subsequent doses as tolerated. The carfilzomib dose on C2D2 was postponed to C2D3 after fever resolved He developed grade 1 diarrhea the day after, and on C2D6 hemoglobin declined from 7.5 to 5.3 g/dl and platelets dropped from 105 × 109 to 5 × 109/l. On C2D15, he presented with fever, diarrhea, cough and tested positive for parainfluenza B virus Three days later, he developed acute kidney injury (creatinine 403 μmol/l from 76 μmol/l) accompanied by thrombocytopenia (platelets 3 × 109/l) and non-immune hemolytic anemia. He had relapsed within 12 months of HDM, while receiving lenalidomide maintenance and was given two cycles of bortezomib-DCEP
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
