105  Broadening the clinical spectrum of bortezimib induced peripheral neuropathy: 4 illustrative cases

Abstract

Bortezomib is a proteasome inhibitor, used in the treatment of multiple myeloma. Bortezimib induced peripheral neuropathy (BIPN) is classically a painful, sensory predominant, length dependent axonal neuropathy [1]. Atypical presentations including demyelinating neuropathies can occur, though rarely (2].We identified 4 patients from the Manchester Centre for Clinical Neuroscience with atypical BIPN. All 4 had multiple myeloma and developed symptoms within 2 cycles of intravenous treatment.Case 1 and 2 developed proximal and distal motor weakness and neuropathic pain. Neurophysiology confirmed mixed demyelinating/axonal neuropathy in both. Cerebral Spinal Fluid analysis confirmed albuminocytological dissociation. Immunomodulatory treatment with IVIg and steroids had minimal effect.Case 3 developed left hand weakness, predominantly affecting the radial musculature with motor conduction block on neurophysiology.Case 4 developed whole body paraesthesias, ataxia and thoracic radicular pain after 2 cycles, neurophysiology confirmed a sensory neuronopathy.Case 2 died due to disease progression, the other 3 cases improved on withdrawal of Bortezimib.ConclusionBIPN can cause neuropathy phenotypes including sensory neuronopathy, motor neuropathy with conduction block and severe demyelinating polyradiculoneuritis. Immunogenic, as well as toxic mechanisms may have a role in the pathogenesis of BIPN.1. Chaudhry V, Cornblath D, Polydefkis M, Ferguson A, Borrello I. Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. Journal of the Peripheral Nervous System. 2008;13(4):275–2822. Thawani S, Tanji K, De Sousa E, Weimer L, Brannagan T. Bortezomib-Associated Demyelinating Neuropathy—Clinical and Pathologic Features. Journal of Clinical Neuromuscular Disease. 2015;16(4):202–209tim.lavin@srft.nhs.uk

Toxic neuropathies: a practical approach

“…Patients experience sharp or burning pain in the extremities, which can be debilitating, often necessitating reducing the dose or stopping the drug. Autonomic involvement has been reported,5 as have other neuropathy phenotypes including distal motor weakness and multifocal motor neuropathy-like presentations 10. Other proteasome inhibitors (carfilzomib, ixazomib) are much less likely to cause neuropathy, and bortezomib given subcutaneously is less likely to cause neuropathy than when given intravenously 1…”