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Abstract: TH-PO0210

Carfilzomib-Associated Thrombotic Microangiopathy in a Patient with Multiple Myeloma: A Diagnostic Dilemma

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Garrastegui Mercado, Emmanuel, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Garcia-Everett, Ashley, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Kanduri, Swetha Rani, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Qunibi, Wajeh Y., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Introduction

Thrombotic microangiopathy (TMA) is classically associated with thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). However, drug-induced forms of TMA are increasingly recognized. Carfilzomib, a proteasome inhibitor approved for refractory myeloma has emerged as a clinically significant cause. Here, we present a case of carfilzomib-associated TMA to emphasize the importance of vigilance in patients receiving this therapy.

Case Description

A 70-year-old woman with high-risk IgG-λ multiple myeloma, characterized by t(14;16) translocation and multiple prior treatment lines, was started on carfilzomib and pomalidomide for relapsed disease. One month into therapy she developed fatigue, anemia (hemoglobin 7.5 g/dL), thrombocytopenia (54×10*9/L) and acute kidney injury (AKI) with serum creatinine increase from 1.3 to 6.4 mg/dL, necessitating dialysis. A urine protein-creatinine ratio of 2 g/g was noted. Initial suspicion centered on light chain cast nephropathy; however, peripheral blood smear revealed schistocytes and laboratory findings showed elevated lactate dehydrogenase, undetectable haptoglobin and absence of a monoclonal protein spike, consistent with TMA. A serological workup for atypical HUS was negative.

Empiric plasma exchange and complement inhibition with eculizumab were initiated. Kidney biopsy was performed with light microscopic features suggestive of acute TMA. Immunofluorescence revealed IgG-κ deposits along the tubular basement membranes discordant with the patient’s known IgG-λ clone and likely reflecting recent eculizumab exposure. Based on the temporal relationship to carfilzomib initiation and exclusion of other etiologies, a diagnosis of carfilzomib- associated TMA was established. Carfilzomib was discontinued and eculizumab was continued at 900 mg weekly . Hematologic parameters and renal function improved after the second dose, and dialysis was discontinued.

Discussion

This case illustrates that AKI in multiple myeloma is not always indicative of disease progression. Carfilzomib-induced TMA should be considered in the differential diagnosis. Early recognition and timely complement inhibition may be critical to reversing hematologic and renal complications, ultimately improving patient outcomes.

Digital Object Identifier (DOI)