GLOMERULAR MICROANGIOPATHY WITH MARKED SYSTEMIC THROMBOTIC MICROANGIOPATHY SHORTLY AFTER BORTEZOMIB IN A NEWLY DIAGNOSED POEMS SYNDROME PATIENT

Abstract

AbstractThe dipeptide boronic acid analogue bortezomib as a potent and selective inhibitor of the proteasome is used for the treatment of plasma cell dyscrasias such as multiple myeloma (MM). Bortezomib may induce glomerular microangiopathy (GMA) with or without systemic thrombotic microangiopathy (TMA) in which vascular endothelial growth factor-nuclear factor (VEGF) -κ B pathway could be involved. MM itself can cause TMA but primarily at presentation. Case reportWe present a case with GMA associated with clinical features supporting systemic TMA shortly after bortezomib. Case: A 54-year-old woman has been diagnosed as having POEMS syndrome. She had symmetric mild degree of peripheral neuropathy, scleroatrophic skin lesions, Raynaud's phenomenon, and retinopathy. IgG kappa type paraproteinemia with a monotypic increase of plasma cells and increased pulmonary artery pressure contributed to the diagnosis. Bortezomib based treatment was started. MethodologyAt the 20th day she developed severe dyspnea. Bilateral pleural effusion and acute kidney failure with thrombocytopenia and microangiopathic hemolytic anemia were documented. Urgent steroid and plasmapheresis were started. ADAMTS13 level proved to be within normal and plasmapheresis did not contribute to improvement. She commenced on hemodialysis and kidney biopsy was decided. Light microscopy findings revealed glomerular capillary thrombus, basement membrane thickening and segmental Resultsduplication. Hyperplastic arteriolar changes were present. No immune deposits were detected by immunofluorescence microscopy. Biopsy findings were diagnostic for thrombotic microangiopathy. The clinical picture deteriorated as sleepiness and confusion. Cranial imaging and cerebrospinal fluid analysis showed no abnormality. Eculizumab with off-label approval contributed to stabilization but no improvement. ConclusionConclusion: Proteasome inhibitors associated with TMA may be life-threatening along with organ dysfunction due to microangiopathy-related ischemia. Membrane attack complex (C5b-9) deposition was found on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease which may point to complement blockade benefit.