Carfilzomib
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Thrombotic microangiopathy: 3 case reports A report described two men and one woman, aged 54–74 years, who developed thrombotic microangiopathy (TMA) during treatment with carfilzomib [not all time to reaction onsets stated] for multiple myeloma (MM) in phase 2 clinical trial (MCRN003/MYX1; NCT02597062). Case 1: A 74-year-old man, who had a history of glaucoma and reflux disease, started receiving IV carfilzomib (20 mg/m2 day 1 cycle 1 then escalated to 70 mg/m2 for all subsequent doses) on days 1, 8 and 15 of a 28 day cycle plus weekly dexamethasone and cyclophosphamide for IgG lambda MM. He started perindopril during cycle seven for new-onset hypertension. During cycle eight following carfilzomib 70 mg/m2, he presented with thrombocytopenia, anaemia and increased creatinine. His BP was 170/82mm Hg. Blood work revealed increased LDH levels, low haptoglobin and schistocytes. A renal biopsy revealed diffuse glomerular involvement by a TMA. Immunofluorescence revealed trace, non-specific glomerular staining for kappa, IgM, and C3. His carfilzomib-based therapy was discontinued. He was then treated with high-dose prednisone. Consequently, he made a complete recovery. Case 2: A 54-year-old woman started receiving receiving IV carfilzomib (20 mg/m2 day 1 cycle 1 then escalated to 70 mg/m2 for all subsequent doses) on days 1, 8 and 15 of a 28 day cycle plus weekly dexamethasone and cyclophosphamide for lambda light chain MM. One day following the second dose of carfilzomib 70 mg/m2, she presented with fever and cough. She had BP of 142/88mm Hg (hypertension). Blood work showed haemoglobin of 63 g/L, platelet count of 3 x 109/L, increased creatinine, low haptoglobin, schistocytes, elevated LDH, increased bilirubin, normal activated partial thromboplastin time and INR. Her carfilzomib-based therapy was discontinued. She was then treated with high-dose prednisone and daily plasma exchange. Consequently, after 3 days, her haemolysis improved. At 2 weeks her complete blood count and creatinine levels normalised. Case 3: A 55-year-old man, who had a history of type 2 diabetes mellitus and hypertension, had been receiving IV carfilzomib (20 mg/m2 day 1 cycle 1 then escalated to 70 mg/m2 for all subsequent doses) on days 1, 8 and 15 of a 28 day cycle plus weekly dexamethasone and cyclophosphamide for IgA kappa MM. During cycle six following carfilzomib 70 mg/m2, he presented with a myalgias, headache and night sweats. He had BP of 120/77mm Hg. Blood work revealed anaemia, thrombocytopenia, schistocytes, increased LDH, normal creatinine, normal activated partial thromboplastin time and INR. His carfilzomibbased therapy was discontinued. He was then treated with high-dose prednisone and plasma exchange for 4 days. Consequently, haemolytic parameters improved and eventually normalized by 6 weeks. Author comment: "Drug-induced thrombotic microangiopathy (DITMA) is a recognized but uncommon complication of proteasome inhibitors." "The unexpectedly high rate (4%) of TMA seen merits further exploration to better understand the et
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