Bortezomib-induced motor neuropathy: A case report

Abstract

Introduction Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma, Waldenström’s macroglobulinemia, mantle cell lymphoma. The most reported adverse effects include fatigue, thrombocytopenia, gastrointestinal symptoms, and peripheral neuropathy, which mostly manifests as sensory neuropathic symptoms. We present a case of a patient who experienced motor neuropathy after initiating treatment with bortezomib. Case report An 87-year-old male was diagnosed with multiple myeloma and started on treatment with bortezomib, dexamethasone, and lenalidomide (VRd). After five cycles of therapy, he developed lower extremity weakness, which was severely debilitating, affecting his ability to walk, and this prompted his visit to the emergency department. Management and outcome The patient was admitted for further workup and underwent electromyography, which was consistent with demyelinating polyneuropathy with active denervation. His symptoms were attributed to bortezomib, and his VRd regimen was held. His symptoms failed to improve despite discontinuation of bortezomib. He then received steroids and intravenous immunoglobulin (IViG) with a gradual resolution of his symptoms. He was thereafter restarted on only lenalidomide and dexamethasone with no recurrence of his neuropathy. Discussion Clinicians need to be aware of the likely risk for motor neuropathy associated with bortezomib. Risk factors like older age and pre-existing neuropathy can predispose patients to this adverse effect, and clinicians should monitor for this toxicity and facilitate dose reduction or discontinuation of therapy if warranted. Sometimes, patients may also need further treatment with steroids or IVIG.

Frequency, nature, severity and preventability of adverse drug reactions arising from cancer chemotherapy in a teaching hospital

“…Another explanation includes the blockage of NF-kB activation which in turn would inhibit nerve growth factors required for neuronal survival. [ 27 ] In our setting, patients with chemotherapy-induced peripheral neuropathy were treated with gabapentin, pregabalin or amitriptyline, which is similar to a study by Grammatico et al 2016. [ 28 ]…”

“…[ 25 ] Case reports regarding bortezomib-induced peripheral neuropathy are available in the literature. [ 26 27 ] The underlying cellular pathway for bortezomib-induced polyneuropathy is nebulous. Other likely explanations would include its targeted activity at the level of mitochondria.…”

Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects

“…Usually, cerebrospinal fluid analysis is not informative [31]. In a handful of individual case series or single case reports, bortezomib was associated with prominent and progressive motor neuropathy [38,40,41,[43][44][45][46][47]. This condition has been ascribed to an immune-mediated mechanism for the frequent finding of albumin-cytological dissociation in the cerebrospinal fluid and for the favorable response to corticosteroids, intravenous immunoglobulin, or plasma exchange [38,40,41,43,[45][46][47].…”

“…Symptoms of autonomic dysfunction, including orthostatic hypotension, postural dizziness, syncope, diarrhea, paralytic ileus, and urinary disturbances have been reported [ 34 , 35 , 36 ] and are likely due to bortezomib toxicity of the pre- and post-ganglionic autonomic nerve fibers of the sympathetic and parasympathetic nervous system [ 34 , 37 , 38 ]. Nerve conduction studies reveal a predominantly axonal or mixed polyneuropathy, although primarily demyelinating features have been occasionally reported [ 39 , 40 , 41 , 42 , 43 ]. Needle electromyography may record neurogenic motor unit potentials with active denervation in the distal muscles of the lower extremities [ 31 ].…”

“…In a handful of individual case series or single case reports, bortezomib was associated with prominent and progressive motor neuropathy [ 38 , 40 , 41 , 43 , 44 , 45 , 46 , 47 ]. This condition has been ascribed to an immune-mediated mechanism for the frequent finding of albumin-cytological dissociation in the cerebrospinal fluid and for the favorable response to corticosteroids, intravenous immunoglobulin, or plasma exchange [ 38 , 40 , 41 , 43 , 45 , 46 , 47 ]. Moreover, in a few patients, a vasculitis process has been observed on nerve pathological examination [ 38 , 47 ].…”