Immune checkpoint inhibitors for patients with pre-existing autoimmune diseases

概要

100th Anniversary of Nagoya J Med Sci: Comments to the Highly Cited Articles
Nagoya J. Med. Sci. 85. 33–34, 2023
doi:10.18999/nagjms.85.1.33

Immune checkpoint inhibitors for patients with pre-existing
autoimmune diseases
Osamu Maeda
Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan

This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Maeda O, Yokota K, Atsuta N, Katsuno M, Akiyama M, Ando Y. Nivolumab for the
treatment of malignant melanoma in a patient with pre-existing myasthenia gravis.
Nagoya J Med Sci. 2016;78(1):119–122.
A 79-year-old man with lymph node recurrence of malignant melanoma received nivolumab,
an antiprogrammed death 1 (PD-1) monoclonal antibody. He had pre-existing ocular myasthenia
gravis (MG) and a continued small amount of corticosteroid. Grade 3 creatine phosphokinase
elevation appeared after two doses of nivolumab, and the treatment was postponed until it
improved to grade 1. After three doses of nivolumab, he experienced diplopia and facial
muscle weakness which were consistent with an acute exacerbation of MG, and the symptoms
relieved without additional treatment for MG. He achieved shrinkage of metastasis after ten
doses of nivolumab. Although a case who died due to MG after administration of nivolumab
was reported recently, pre-existing MG is considered not to be always a contraindication of
nivolumab.
Keywords: malignant melanoma, nivolumab, anti-programmed death 1 (PD-1) monoclonal
antibody, myasthenia gravis, creatine phosphokinase
In an earlier case report, we described the use of the immune checkpoint inhibitor nivolumab
to treat a patient with malignant melanoma who was comorbid with myasthenia gravis.1 During
this course of treatment, the patient’s myasthenia gravis symptoms worsened, improving only with
the temporary withdrawal of nivolumab. Nevertheless, the malignant melanoma decreased in size.
Patients with pre-existing autoimmune diseases are usually excluded from the clinical trials
of immune checkpoint inhibitors based on the study’s exclusion criterion.2 However, in clinical
practice, the administration of immune checkpoint inhibitors in such patients is still controversial.
The mentioned case report has been cited in other publications, a few of which discussed cases of
myasthenia gravis induced by immune checkpoint inhibitors,3,4 while the others elaborated on the
Received: September 27, 2022; accepted: October 24, 2022
Corresponding Author: Osamu Maeda, MD, PhD
Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital,
65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan
Tel: +81-52-744-1903, Fax: +81-52-744-1903, E-mail: maeda-o@med.nagoya-u.ac.jp
33

Osamu Maeda

pros and cons of administering immune checkpoint inhibitors to cancer patients with autoimmune
diseases.5 In clinical cases of cancer, treatment decisions take risk–benefit ratio into account.
However, for certain cancers, other therapies were frequently used when these were available as
alternative options to immune checkpoint inhibitors. Moreover, immune checkpoint inhibitors are
often administered with caution in diseases like malignant melanoma for which few therapeutic
options are available. The indications for immune checkpoint inhibitors are broadening for many
types of cancer. As a result, weighing the choice to use immune checkpoint inhibitors in patients
with pre-existing autoimmune diseases is likely to become more challenging for clinicians.
We extend our congratulations to the Nagoya Journal of Medical Science on its 100th anniversary and hope that the journal will continue to grow and develop by publishing interesting
and significant findings.

REFERENCES
  1

Maeda O, Yokota K, Atsuta N, Katsuno M, Akiyama M, Ando Y. Nivolumab for the treatment of malignant
melanoma in a patient with pre-existing myasthenia gravis. Nagoya J Med Sci. 2016;78(1):119–122.
 2 Rzeniewicz K, Larkin J, Menzies AM, Turajlic S. Immunotherapy use outside clinical trial populations:
never say never? Ann Oncol. 2021;32(7):866–880. doi:10.1016/j.annonc.2021.03.199.
 3 Makarious D, Horwood K, Coward JIG. Myasthenia gravis: an emerging toxicity of immune checkpoint
inhibitors. Eur J Cancer. 2017;82:128–136. doi:10.1016/j.ejca.2017.05.041.
  4 Suzuki S, Ishikawa N, Konoeda F, et al. Nivolumab-related myasthenia gravis with myositis and myocarditis
in Japan. Neurology. 2017;89(11):1127–1134. doi:10.1212/WNL.0000000000004359.
 5 Abdel-Wahab N, Shah M, Lopez-Olivo MA, Suarez-Almazor ME. Use of immune checkpoint inhibitors in
the treatment of patients with cancer and preexisting autoimmune disease: a systematic review. Ann Intern
Med. 2018;168(2):121–130. doi:10.7326/M17-2073.
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