Partial Response to Nivolumab and Ipilimumab in a Patient With Malignant Pleural Mesothelioma and Pre-Existing Myasthenia Gravis Without Severe Flares or Immune-Related Adverse Events: A Case Report

Our plain-English summary of Partial Response to Nivolumab and Ipilimumab in a Patient With Malignant Pleural Mesothelioma and Pre-Existing Myasthenia Gravis Without Severe Flares or Immune-Related Adverse Events: A Case Report, by M. Higa, T. Kuda, Y. Ohya, et al (Respirology Case Reports, 2025).

The study

• Authors: M. Higa, T. Kuda, Y. Ohya, H. Kawasaki
• Journal: Respirology Case Reports
• Published: 2025;13(8):e70297
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Detailed clinical data on the combination immune checkpoint inhibitor (ICI) therapy in patients with myasthenia gravis (MG) remain limited. We report a case of malignant pleural mesothelioma with previously undiagnosed ocular MG. Owing to hepatic dysfunction, reduced doses of nivolumab and ipilimumab were administered before confirmation of anti-acetylcholine receptor (AChR) antibody positivity. MG was diagnosed based on subtle ocular symptoms and serological tests. Prophylactic intravenous immunoglobulin and an acetylcholinesterase inhibitor were administered; combination therapy was discontinued owing to the risk of MG flare, but a partial tumour response was achieved. With disease progression, nivolumab monotherapy was reintroduced, and early steroid pulse therapy was administered owing to elevated creatine kinase, again inducing a partial response. Serological screening for anti-AChR antibodies may help prevent severe MG flares and immune-related adverse events. With caution, dose-reduced and limited-exposure ICI combination therapy may be feasible in selected patients with MG under appropriate prophylactic management.

© 2025 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.

In plain English

This case report described one man in his 70s with stage IIIB biphasic malignant pleural mesothelioma that had spread into the liver, treated by authors at a hospital in Okinawa, Japan. The article does not mention asbestos exposure. He received reduced doses of the immune drugs nivolumab (240 mg) and ipilimumab (0.5 mg/kg) because of liver problems. The day after the infusion, a blood test came back positive for antibodies linked to myasthenia gravis, an autoimmune nerve-muscle disease. He was diagnosed with a mild eye-only form he had not noticed and was given preventive intravenous immunoglobulin and ambenonium chloride. The immune drugs were stopped because of the risk of a flare. His myasthenia stayed stable, and the tumour partly shrank until about Day 130, when it grew again. After chemotherapy, nivolumab alone was given. A muscle enzyme rose to 861 U/L, he received three days of high-dose steroids, and the tumour partly shrank again. The authors concluded that, with caution, combination therapy may be feasible in selected patients with myasthenia gravis when given at reduced doses, with limited exposure and with appropriate preventive measures.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (one patient)
• Who was studied: One man in his 70s with stage IIIB biphasic malignant pleural mesothelioma and liver invasion, who also had previously undiagnosed ocular myasthenia gravis. The authors are based at NHO Okinawa Hospital, Japan. Treatment dates are not given.
• Exposure: The article reports no asbestos or occupational exposure. The treatment described was nivolumab plus ipilimumab, reduced from the standard 360 mg and 1 mg/kg to 240 mg and 0.5 mg/kg because of liver dysfunction. Later, nivolumab 240 mg was given alone.
• Main results:
  • After the first combination infusion, anti-acetylcholine receptor antibody positivity was confirmed. With double vision and a drooping left eyelid that had been present for 4 to 5 years, the patient was diagnosed with pre-existing ocular myasthenia gravis (MG Foundation of America class I).
  • To prevent worsening, intravenous immunoglobulin (total 2 g/kg) was given on Days 8 to 12, and oral ambenonium chloride was started on Day 15.
  • Frequent premature heartbeats occurred on Days 18 to 22. Tests were normal (creatine kinase 59 to 73 U/L, troponin T negative, ejection fraction 64%), the arrhythmias resolved after Day 23, and myocarditis was ruled out.
  • Immune therapy was stopped because of flare risk. Myasthenia symptoms stayed stable without worsening, and ambenonium chloride was stopped on Day 44.
  • The tumour had shrunk by Day 14 and a partial response was maintained through Day 101. By Day 130 the basal lung mass had enlarged, which was classed as progressive disease.
  • Six cycles of cisplatin and pemetrexed gave stable disease as the best response.
  • After nivolumab 240 mg alone, the patient had no symptoms, but creatine kinase rose to 861 U/L on Day 7. Methylprednisolone 1 g/day was given for 3 days, and creatine kinase levels normalised.
  • Under nivolumab monotherapy, a partial response was seen again, with the basal lung mass shrinking by Day 45 and the response sustained through Day 114.
• The authors' conclusion: The authors concluded that, although caution is warranted, combination immune checkpoint inhibitor therapy may be feasible in selected patients with myasthenia gravis when given with dose reductions, limited exposure and appropriate preventive measures. They also wrote that antibody screening enabled timely detection of myasthenia gravis in this case.

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Ipilimumab (Yervoy), Pleural Mesothelioma, Immune-Related Adverse Events, checkpoint inhibitors, Disease Progression.

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