Deterioration in multifocal motor neuropathy upon treatment of immune-related adverse events of checkpoint inhibition

Abstract

Immune checkpoint inhibitors (ICIs) have significantly improved the clinical outcome in multiple types of advanced or metastatic malignancies and are prescribed increasingly. However, immune-related adverse events (irAEs) occur frequently. Here, we present a patient with multifocal motor neuropathy and melanoma, with worsening of muscle weakness upon ICI therapy and concomitant use of steroids for the treatment of hepatitis, which was considered an irAE. Upon treatment with highly dosed immunoglobulins and steroid tapering, the patients' muscular symptoms improved while hepatitis resolved. This case highlights the importance of careful evaluation of patients with multifocal motor neuropathy treated with ICIs, highlights the risks of treatment with steroids in multifocal motor neuropathy patients and suggests an alternative treatment of irAEs with intravenous immunoglobulins.

Executive summary

Background

• Immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) occur frequently.

• Clinical trials on ICIs have largely excluded patients with a history of autoimmune diseases because of the risk of treatment-induced irAEs and exacerbation of the underlying autoimmune disease.

• In real-world, worsening of autoimmune disease occurs frequently during ICI treatment.

Case description

• We present a patient with multifocal motor neuropathy (MMN), an autoimmune disease mediated by anti-GM1 antibodies, who suffered from increased muscle weakness during treatment with ICIs for melanoma.

Discussion

• Patients with MMN might be at risk for worsening of their underlying disease upon ICI treatment.

• First-line treatment of irAEs are steroids, however, in MMN, this could cause clinical deterioration.

Conclusion

• It is advised to not use steroids in MMN patients, instead, IVIgs could be considered for the treatment of irAEs.

• MMN patients should be closely monitored during ICI therapy.

Keywords: :

• clinical deterioration
• immune checkpoint inhibition
• immune-related adverse events
• immunotherapy
• multifocal motor neuropathy

Author contributions

VEA Kleinveld: Formulation of research aims, preparation of the initial draft and revisions, project administration. A Hotter: Formulation of research aims, supervision, revision of manuscript. WN Löscher: Formulation of research aims, supervision, revision of manuscript. J Wanschitz: Formulation of research aims, supervision, revision of manuscript. CGC Horlings: Formulation of research aims, supervision, revision of manuscript.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Informed consent disclosure

The authors state that they have obtained verbal and written informed consent from the patient/patients for the inclusion of their medical and treatment history within this case report.