Immune-mediated neuropathies in myeloma patients treated with bortezomib

Sabrina Ravaglia, Alessandro Corso, Giovanni Piccolo, Alessandro Lozza, Enrico Alfonsi, Silvia Mangiacavalli, Marzia Varettoni, Patrizia Zappasodi, Arrigo Moglia, Mario Lazzarino, Alfredo Costa

Research output: Contribution to journalArticle

Abstract

Objective: Bortezomib is a new chemotherapeutic drug available for the treatment of lymphoid disorders, including multiple myeloma. Although its primary mechanism of action is proteasome inhibition, other mechanisms can contribute to the therapeutic effects, including modulation of inflammatory cytokines and immune response. One of the main toxic effects of bortezomib is peripheral neuropathy, usually occurring in the form of a painful, sensory axonal neuropathy. The mechanisms of peripheral damage, however, are still unclear. We here report a series of patients treated with bortezomib, who developed a peripheral damage possibly related to immuno-mediated, rather than toxic, mechanisms. Methods: Five patients who developed a peripheral neuropathy with severe motor involvement under bortezomib treatment underwent CSF, electrophysiological, and spinal cord MRI examinations. Results: Peripheral damage was characterized by: demyelinating or mixed axonal-demyelinating neuropathy, with prominent motor involvement; albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients; favourable outcome in 4/5 patients after immune treatments, either steroids (2 patients) or IVIg (2 patients). Conclusions: In some instances, the peripheral damage associated with bortezomib may recognize immuno-mediated mechanisms. Significance: This form of bortezomib-associated neuropathy needs to be recognized as treatable condition, as it may respond to immune therapies. Unexplained worsening of neurological dysfunction despite bortezomib discontinuation, with prominent motor involvement and CSF signs of inflammation, may be the clues to this complication.

Original languageEnglish
Pages (from-to)2507-2512
Number of pages6
JournalClinical Neurophysiology
Volume119
Issue number11
DOIs
Publication statusPublished - Nov 2008

Fingerprint

Poisons
Peripheral Nervous System Diseases
Therapeutic Uses
Proteasome Endopeptidase Complex
Therapeutics
Bortezomib
Multiple Myeloma
Albumins
Spinal Cord
Steroids
Cytokines
Inflammation
Pharmaceutical Preparations

Keywords

  • Bortezomib
  • IVIg
  • Multiple myeloma
  • Peripheral neuropathy
  • Polyradiculoneuritis

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)
  • Neurology
  • Sensory Systems

Cite this

Immune-mediated neuropathies in myeloma patients treated with bortezomib. / Ravaglia, Sabrina; Corso, Alessandro; Piccolo, Giovanni; Lozza, Alessandro; Alfonsi, Enrico; Mangiacavalli, Silvia; Varettoni, Marzia; Zappasodi, Patrizia; Moglia, Arrigo; Lazzarino, Mario; Costa, Alfredo.

In: Clinical Neurophysiology, Vol. 119, No. 11, 11.2008, p. 2507-2512.

Research output: Contribution to journalArticle

@article{b00597b392d44f8990eeca959245144b,
title = "Immune-mediated neuropathies in myeloma patients treated with bortezomib",
abstract = "Objective: Bortezomib is a new chemotherapeutic drug available for the treatment of lymphoid disorders, including multiple myeloma. Although its primary mechanism of action is proteasome inhibition, other mechanisms can contribute to the therapeutic effects, including modulation of inflammatory cytokines and immune response. One of the main toxic effects of bortezomib is peripheral neuropathy, usually occurring in the form of a painful, sensory axonal neuropathy. The mechanisms of peripheral damage, however, are still unclear. We here report a series of patients treated with bortezomib, who developed a peripheral damage possibly related to immuno-mediated, rather than toxic, mechanisms. Methods: Five patients who developed a peripheral neuropathy with severe motor involvement under bortezomib treatment underwent CSF, electrophysiological, and spinal cord MRI examinations. Results: Peripheral damage was characterized by: demyelinating or mixed axonal-demyelinating neuropathy, with prominent motor involvement; albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients; favourable outcome in 4/5 patients after immune treatments, either steroids (2 patients) or IVIg (2 patients). Conclusions: In some instances, the peripheral damage associated with bortezomib may recognize immuno-mediated mechanisms. Significance: This form of bortezomib-associated neuropathy needs to be recognized as treatable condition, as it may respond to immune therapies. Unexplained worsening of neurological dysfunction despite bortezomib discontinuation, with prominent motor involvement and CSF signs of inflammation, may be the clues to this complication.",
keywords = "Bortezomib, IVIg, Multiple myeloma, Peripheral neuropathy, Polyradiculoneuritis",
author = "Sabrina Ravaglia and Alessandro Corso and Giovanni Piccolo and Alessandro Lozza and Enrico Alfonsi and Silvia Mangiacavalli and Marzia Varettoni and Patrizia Zappasodi and Arrigo Moglia and Mario Lazzarino and Alfredo Costa",
year = "2008",
month = "11",
doi = "10.1016/j.clinph.2008.08.007",
language = "English",
volume = "119",
pages = "2507--2512",
journal = "Clinical Neurophysiology",
issn = "1388-2457",
publisher = "Elsevier Ireland Ltd",
number = "11",

}

TY - JOUR

T1 - Immune-mediated neuropathies in myeloma patients treated with bortezomib

AU - Ravaglia, Sabrina

AU - Corso, Alessandro

AU - Piccolo, Giovanni

AU - Lozza, Alessandro

AU - Alfonsi, Enrico

AU - Mangiacavalli, Silvia

AU - Varettoni, Marzia

AU - Zappasodi, Patrizia

AU - Moglia, Arrigo

AU - Lazzarino, Mario

AU - Costa, Alfredo

PY - 2008/11

Y1 - 2008/11

N2 - Objective: Bortezomib is a new chemotherapeutic drug available for the treatment of lymphoid disorders, including multiple myeloma. Although its primary mechanism of action is proteasome inhibition, other mechanisms can contribute to the therapeutic effects, including modulation of inflammatory cytokines and immune response. One of the main toxic effects of bortezomib is peripheral neuropathy, usually occurring in the form of a painful, sensory axonal neuropathy. The mechanisms of peripheral damage, however, are still unclear. We here report a series of patients treated with bortezomib, who developed a peripheral damage possibly related to immuno-mediated, rather than toxic, mechanisms. Methods: Five patients who developed a peripheral neuropathy with severe motor involvement under bortezomib treatment underwent CSF, electrophysiological, and spinal cord MRI examinations. Results: Peripheral damage was characterized by: demyelinating or mixed axonal-demyelinating neuropathy, with prominent motor involvement; albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients; favourable outcome in 4/5 patients after immune treatments, either steroids (2 patients) or IVIg (2 patients). Conclusions: In some instances, the peripheral damage associated with bortezomib may recognize immuno-mediated mechanisms. Significance: This form of bortezomib-associated neuropathy needs to be recognized as treatable condition, as it may respond to immune therapies. Unexplained worsening of neurological dysfunction despite bortezomib discontinuation, with prominent motor involvement and CSF signs of inflammation, may be the clues to this complication.

AB - Objective: Bortezomib is a new chemotherapeutic drug available for the treatment of lymphoid disorders, including multiple myeloma. Although its primary mechanism of action is proteasome inhibition, other mechanisms can contribute to the therapeutic effects, including modulation of inflammatory cytokines and immune response. One of the main toxic effects of bortezomib is peripheral neuropathy, usually occurring in the form of a painful, sensory axonal neuropathy. The mechanisms of peripheral damage, however, are still unclear. We here report a series of patients treated with bortezomib, who developed a peripheral damage possibly related to immuno-mediated, rather than toxic, mechanisms. Methods: Five patients who developed a peripheral neuropathy with severe motor involvement under bortezomib treatment underwent CSF, electrophysiological, and spinal cord MRI examinations. Results: Peripheral damage was characterized by: demyelinating or mixed axonal-demyelinating neuropathy, with prominent motor involvement; albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients; favourable outcome in 4/5 patients after immune treatments, either steroids (2 patients) or IVIg (2 patients). Conclusions: In some instances, the peripheral damage associated with bortezomib may recognize immuno-mediated mechanisms. Significance: This form of bortezomib-associated neuropathy needs to be recognized as treatable condition, as it may respond to immune therapies. Unexplained worsening of neurological dysfunction despite bortezomib discontinuation, with prominent motor involvement and CSF signs of inflammation, may be the clues to this complication.

KW - Bortezomib

KW - IVIg

KW - Multiple myeloma

KW - Peripheral neuropathy

KW - Polyradiculoneuritis

UR - http://www.scopus.com/inward/record.url?scp=54149104958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54149104958&partnerID=8YFLogxK

U2 - 10.1016/j.clinph.2008.08.007

DO - 10.1016/j.clinph.2008.08.007

M3 - Article

C2 - 18829381

AN - SCOPUS:54149104958

VL - 119

SP - 2507

EP - 2512

JO - Clinical Neurophysiology

JF - Clinical Neurophysiology

SN - 1388-2457

IS - 11

ER -