P034 Checkpoint inhibitor-induced coexisting myositis and myasthenia gravis in a malignant mesothelioma patient: a case report
Authors: Javaid Farhan , Byravan Swetha , Makan Sandeep , Kadicheeni Meeriam , Neame Rebecca , Durrani Maumer 
Published: April 2022

Abstract

Background/Aims
Nivolumab & ipilimumab are immune checkpoint inhibitors (ICIs) and combination therapy has shown efficacy in patients with malignant pleural mesothelioma. Nivolumab is a fully human IgG4 monoclonal antibody known as a programmed cell death 1 (PD-1) immune checkpoint inhibitor. The combination therapy nivolumab & ipilimumab features a potentially synergistic mechanism of action that targets 2 different checkpoints (PD-1 and CTLA-4) respectively. Myositis, an immune-related adverse event, has been reported in the literature. Ipilimumab and nivolumab have also been associated with the development/exacerbation of myasthenia gravis (MG).

Methods
A 75-year-old woman with right sarcomatoid malignant mesothelioma presented to the hospital with muscle cramps and a raised creatinine kinase, a few weeks after initiation of nivolumab & ipilimumab. In addition to myalgia and proximal limb weakness, her symptoms progressed to involve new right eye ptosis, double vision, and dysphagia. She was diagnosed with ICI-related myositis after an EMG was suggestive of myositis, but antibody screens for myositis and myasthenia gravis were negative. Treatment was started with intravenous methylprednisolone and subsequently was treated with IVIG and mycophenolate mofetil 1g twice daily alongside the tapering oral steroids for maintenance, leading to resolution of proximal muscle weakness caused by immunotherapy-induced myositis. Following the initial improvement of muscle weakness, reassessment revealed worsening bulbar symptoms including ptosis, dysphagia, and diplopia. She was therefore readmitted. As her creatinine kinase, muscle weakness and CRP had now normalized, the impression at this stage was of symptoms predominantly related to myasthenia gravis rather than of myositis flare-up. Pyridostigmine was commenced as a trial, which demonstrated improvement with regards to the ptosis.

Results
ICIs have led to the development of new approaches for cancer treatment with positive outcomes. However, checkpoint blockade is associated with a unique spectrum of immune-related adverse events, which may cause irreversible neurological deficits and even death. This is a rare reported case of a patient developing nivolumab & ipilimumab-induced myositis concomitant with new-onset MG after treatment for advanced mesothelioma. Additional studies are needed to explore the association between myositis, MG, and ICI therapy. This woman is having ongoing multidisciplinary management involving oncologists, rheumatologists, and neurologists. She continues to be treated with mycophenolate mofetil and pyridostigmine. Ipilimumab and nivolumab were permanently discontinued.

Conclusion
This case demonstrates that rheumatologists must be alert to the possibility of myositis overlapping with MG in patients treated with checkpoint inhibitors who develop weakness. Early recognition complete evaluation and a team approach are essential in such a complex case.

Disclosure
F. Javaid: None. S. Byravan: None. S. Makan: None. M. Kadicheeni: None. R. Neame: None. M. Durrani: None.