Ophthalmoplegia and HyperCKemia in a patient with recurrent thymoma and PD-1 blocking treatment

 

We report a 62-year old female patient who presented with proximal weakness and hyperCKemia (10.564 U/l) after initiation of treatment with the anti-PD1 checkpoint inhibitor pembrolizumab due to recurrent thymoma. The thymoma (Masaoka stage III) had first been diagnosed in 2013 and treated with radiotherapy after surgery. She had no myasthenic symptoms. Recurrence of the thymoma occurred in 2017 with pleural and peritoneal carcinomatosis. Therapy with high dose steroids was started immediately after the occurrence of muscle weakness, but the patient developed severe impairment of eye movements and the limb weakness progressed. Electrophysiological assessment showed an irritable myopathy, neurography was normal and repetitive nerve stimulation revealed no decrement. Although AChR antibodies were detectable, inhibition of acetylcholinesterase with edrophoniumchloride had no effect on eye movements or limb weakness. Anti-GQ1b antibodies were negative. A cranial MRI did not confirm inflammation of extraocular muscles. Following immunosuppressive treatment with Cyclosporin A, a subsequent treatment with 6 cycles PAC chemotherapy (dosis reduced regimen) and a recent switch to everolimus the patient is in a stable condition with mild proximal weakness and almost complete resolution of ophthalmoplegia.

This case illustrates complex immune-mediated neuromuscular complications of PD-1 blocking agents causing clinical manifestations that may differ from classical phenotypes.