Bortezomib-Associated Demyelinating Neuropathy—Clinical and Pathologic Features

Thawani, Sujata; Tanji, Kurenai; Sousa, Eduardo A. De; Weimer, Louis H.; Brannagan, Thomas H.

doi:10.1097/cnd.0000000000000077

Cited by 35 publications

(28 citation statements)

References 24 publications

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“…Nerve conduction studies (NCS) usually show a predominantly sensory or mixed axonal polyneuropathy, despite mixed or primarily demyelinating features having been occasionally reported, most in the setting of clinical patterns resembling Guillain‐Barré Syndrome (see below). Typical NCS findings in patients with BIPN include: low or absent sensory action potentials amplitude, and reduced peroneal compound muscle action potential (CMAP) in more severe cases.…”

Section: Clinical Phenotypementioning

confidence: 99%

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Velasco

Alberti

Bruna

et al. 2019

J Peripheral Nervous Sys

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Proteasome inhibitors (PIs), especially bortezomib (BTZ), have come to the forefront over the last years because of their unprecedented efficacy mainly against multiple myeloma (MM). Unfortunately, peripheral neuropathy (PN) secondary to treatment of MM with PIs has emerged as a clinically relevant complication, which negatively impacts the quality of life of MM survivors. Bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, which develops in 30% to 60% of patients during treatment. Typically, BIPN is a length-dependent sensory axonopathy characterized by numbness, tingling, and severe neuropathic pain in stocking and glove distribution. BIPN mechanisms have not yet been fully elucidated. Experimental studies suggest that aggresome formation, endoplasmic reticulum stress, myotoxicity, microtubule stabilization, inflammatory response, and DNA damage could contribute to this neurotoxicity. A new generation of structurally distinct PIs has been developed, being increasingly used in clinical settings. Carfilzomib exhibits a much lower neurotoxicity profile, with a significantly lower incidence of PN compared to BTZ. Pre-existing PN increases the risk of developing BIPN. Besides, BIPN is related to dose, schedule and mode of administration and modifications of these factors have lowered the incidence of PN. However, to date there is no cure for PIs-induced PN (PIIPN), and a careful neurological monitoring and dose adjustment is a key strategy for preserving quality of life. This review critically looks at the pathogenesis, incidence, risk factors, both clinical and pharmacogenetics, clinical phenotype and management of PIIPN. We also make recommendations for further elucidating the whole clinical spectrum of PIIPN. K E Y W O R D S bortezomib, carfilzomib, peripheral neuropathy, peripheral neurotoxicity, proteasome inhibitor-induced neuropathy 1 | INTRODUCTION Inhibition of proteasome function has emerged as an efficacious strategy with a robust rationale in anticancer therapy. Proteasome inhibitor (PI)-based regimens have become an integral component of the treatment of multiple myeloma (MM), a malignancy of plasma cells accounting for approximately 1% of cancers and 12% of hematological malignancies. Bortezomib (BTZ) was the first approved PI and to date has become the standard of anti-myeloma 1 and mantle cell lymphoma therapies. 2 Postmarketing trials of BTZ quickly pointed to PN as its main nonhematological, dose-limiting toxicity of BTZ. Similar to clinical trial results, the use of BTZ in real-world oncology practice documented that BTZ-induced peripheral neuropathy (BIPN) develops in up to 50% of BTZ-treated MM patients. 3,4 PN due to MM treatment

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Section: Clinical Phenotypementioning

confidence: 99%

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Velasco

Alberti

Bruna

et al. 2019

J Peripheral Nervous Sys

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“…Peripheral nerve changes and polyneuropathy symptoms affect 20–30% of all bortezomib‐treated patients and are manifested as neuropathic pain of toes and/or fingers, tingling and burning sensations, and muscle wasting. Electrophysiological studies show a slight decrease in motor and sensory nerve conduction velocity, H‐reflex prolonged latency and sensory potential low amplitude suggestive of either axonal or demyelination neuropathy (Carozzi et al., 2013; Corso et al., 2010; Thawani, Tanji, De Sousa, Weimer, & Brannagan, 2015). The mechanism of bortezomib‐induced polyneuropathy remains elusive.…”

Section: Bortezomibmentioning

confidence: 99%

Chemotherapy‐induced neuropathies—a growing problem for patients and health care providers

2016

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IntroductionChemotherapy‐induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti‐cancer drugs are: platinum‐based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids.MethodsHere, in this paper, based on our experience and current knowledge, we provide a short review of the most common, neuropathy‐inducing anti‐cancer drugs, describe the most prevalent neuropathy symptoms produced by each of them, and outline preventive measures and treatment guidelines for cancer patients suffering from neuropathy and for their health care providers.ResultsPatients should be encouraged to report any signs of neuropathic pain, alteration in sensory perception, tingling, numbness, burning, increased hot/cold sensitivity and motor dysfunctions as early as possible. If known neurotoxic chemotherapeutics are used, a neurological examination with electrophysiological evaluation should be implemented early in the course of treatment so, both patients and physicians would be better prepared to cope with possible neurotoxic effects.ConclusionsThe use of neurotoxic chemotherapeutics should be closely monitored and if clinically permitted, that is, if a patient shows signs of cancer regression, drug doses should be reduced or combined with other less neurotoxic anti‐cancer medication. If not counteractive, the use of over the counter antineuropathic supplements such as calcium or magnesium might be encouraged. If physically possible, patients should also be encouraged to exercise regularly and avoid factors that might increase nerve damage such as excessive drinking, smoking, or sitting in a cramped position.

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“…Такая частота встречаемости бортезомиб-ассоцирован-ной полинейропатии при ММ близка к той, которая при-водится в работах других авторов [24,25].…”

Section: Discussionunclassified

Clinical characteristics of pain syndrome in patients with multiple myeloma

Stamo¹,

Grigorieva²

2016

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Bortezomib-Associated Demyelinating Neuropathy—Clinical and Pathologic Features

Abstract: Although most toxic neuropathies are symmetrical axonal neuropathies, bortezomib is part of a small list of agents that may cause a demyelinating polyneuropathy and axonal degeneration. These findings have been confirmed by nerve biopsy.

Cited by 35 publications

References 24 publications

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Bortezomib and other proteosome inhibitors—induced peripheral neurotoxicity: From pathogenesis to treatment

Chemotherapy‐induced neuropathies—a growing problem for patients and health care providers

Clinical characteristics of pain syndrome in patients with multiple myeloma

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