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Der Nervenarzt

, Volume 90, Issue 2, pp 138–147 | Cite as

Neurologische Nebenwirkungen von Checkpoint-Inhibitoren

  • S. Knauss
  • L. Ginesta Roque
  • P. Hühnchen
  • L. Heinzerling
  • W. BöhmerleEmail author
  • M. Endres
Übersichten

Zusammenfassung

Hintergrund

In den letzten Jahren wurde die Therapie zahlreicher Tumorentitäten durch den Einsatz moderner Immuntherapien mit Checkpoint-Inhibitoren revolutioniert. Guten Ansprechraten stehen jedoch zahlreiche immunvermittelte Nebenwirkungen gegenüber. Neurologische immunvermittelte Nebenwirkungen gehören zu den seltenen, jedoch häufig schwer verlaufenden Komplikationen einer Checkpoint-Inhibitor-Therapie.

Methode

Es wurde eine systematische Suche in den Datenbanken PubMed und Web of Science nach Fallberichten und Studien zu neurologischen Nebenwirkungen unter Checkpoint-Inhibitor-Therapie durchgeführt.

Ergebnisse

Insgesamt 42 Arbeiten zu neurologischen Nebenwirkungen von Checkpoint-Inhibitoren mit insgesamt 85 berichteten Fällen wurden identifiziert. Die häufigsten berichteten neurologischen Nebenwirkungen waren Myopathien, Neuropathien, Erkrankungen der neuromuskulären Endplatte und Enzephalitiden. Die höchste Morbidität und Mortalität wiesen Enzephalopathien und Myopathien mit begleitender Myokarditis auf.

Schlussfolgerung

Vor dem Hintergrund eines rasch zunehmenden Einsatzes von Checkpoint-Inhibitoren gibt diese Arbeit einen Überblick über bislang berichtete klinische Verlaufsformen neurologischer Nebenwirkungen. Kontrollierte Studien zur Therapie neurologischer Nebenwirkungen fehlen. Fallberichte lassen vermuten, dass eine frühzeitige Steroidtherapie die Wahrscheinlichkeit einer kompletten Remission der neurologischen Symptome erhöht. Typische Symptomkonstellationen müssen daher schnell erkannt und eine immunsuppressive Therapie eingeleitet werden.

Schlüsselwörter

Enzephalitisches Syndrom Multiple Sklerose Tumoren Neuropathien Myopathien 

Abkürzungen

AChR

Acetylcholin-Rezeptor

CD28

„Cluster of differentation 28“

CD80

„Cluster of differentiation 80“

CD86

„Cluster of differentiation 86“

CIDP

Chronisch inflammatorische demyelinisierende Polyneuropathie

CK

Kreatinkinase

CTLA-4

„Cytotoxic T‑lymphocyte-associated protein 4, cytotoxic T lymphocyte antigen 4“

DMMR

„Mismatch repair deficient“

EMG

Elektromyographie

FDA

Food and Drug Administration

GBS

Guillain-Barré-Syndrom

irAE

„Immune related adverse events“

IVIg

Intravenöse Gabe von Immunglobulinen

MERS

„Mild encephalopathy with a reversible splenial lesion“

MRT

Magnetresonanztomographie

MSI-H

„Microsatellite instability-high“

NK-Zellen

Natürliche Killerzellen

NMDA

N-Methyl-D-Aspartat

PD-1

„Programmed cell death-1“

PD-L1

„Programmed cell death-ligand 1“

PD-L2

„Programmed cell death-ligand 2“

PNS

Peripheres Nervensystem

PPH

Plasmapherese

PRES

Posterior reversible encephalopathy syndrome

SREAT

Steroid responsive encephalopathy associated with autoimmune thyroiditis

ZNS

Zentrales Nervensystem

Neurological side effects of checkpoint inhibitors

Abstract

Background

In recent years the treatment of many tumor entities has been revolutionized by the use of modern immunotherapies with checkpoint inhibitors; however, good response rates are contrasted by many immune-mediated side effects. Neurological immune-mediated side effects are rare but often severe complications of checkpoint inhibitor treatment.

Method

A systematic search in the PubMed and Web of Sciences databases was carried out for case reports and studies on neurological side effects during checkpoint inhibitor treatment.

Results

A total of 42 articles on neurological side effects of checkpoint inhibitors with a total of 85 reported cases could be identified. The most frequently reported neurological side effects were myopathies, neuropathies, diseases of the neuromuscular endplates and encephalitides. Among those, encephalitides and myopathies with accompanying myocarditis were associated with the highest morbidity and mortality.

Conclusion

Against the background of a rapidly increasing use of checkpoint inhibitors, this article provides an overview of currently available reports on the clinical courses of neurological side effects. Controlled studies on the treatment of neurological side effects are lacking. From case studies it can be assumed that early steroid treatment increases the probability of a complete remission of neurological symptoms. Typical symptom constellations must therefore be rapidly recognized and an immunosuppressive treatment must be initiated.

Keywords

Encephalitis Multiple sclerosis Tumors Neuropathies Myopathies 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

S. Knauss, L. Ginesta Roque, P. Hühnchen, L. Heinzerling, W. Böhmerle und M. Endres geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Supplementary material

115_2018_571_MOESM1_ESM.pdf (36 kb)
1. Selektionsprozess während der Literaturrecherche
115_2018_571_MOESM2_ESM.pdf (8 kb)
2. Hintergrund der Checkpoint-Inhibitor-Therapie
115_2018_571_MOESM3_ESM.pdf (172 kb)
3. Zusätzliche Tabelle: Neurologische Nebenwirkungen nach Substanzklassen
115_2018_571_MOESM4_ESM.pdf (16 kb)
4. Zusätzliche Tabelle: Neurologische Nebenwirkungen in den Zulassungsstudien

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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • S. Knauss
    • 1
  • L. Ginesta Roque
    • 1
  • P. Hühnchen
    • 1
  • L. Heinzerling
    • 2
  • W. Böhmerle
    • 1
    Email author
  • M. Endres
    • 1
    • 3
    • 4
    • 5
  1. 1.Klinik für Neurologie mit Experimenteller NeurologieCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBerlinDeutschland
  2. 2.HautklinikUniversitätsklinikum ErlangenErlangenDeutschland
  3. 3.Center for Stroke Research BerlinCharité-Universitätsmedizin BerlinBerlinDeutschland
  4. 4.Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)BerlinDeutschland
  5. 5.Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)BerlinDeutschland

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