Reactions Weekly | 2021
Pembrolizumab/pyridostigmine
Abstract
Various toxicities and drug ineffectiveness: case report A 75-year-old woman developed myasthenia gravis-like disorder, ocular myositis and hepatitis during treatment with pembrolizumab for high-grade urothelial carcinoma of the left ureter. She also exhibited drug ineffectiveness while receiving treatment with pyridostigmine for myasthenia gravis-like disorder [not all routes stated]. The woman, who had a history of hyperlipidaemia, hypertension and type II diabetes mellitus, presented with unilateral left leg oedema and painless haematuria. After examination, she was diagnosed with high-grade urothelial carcinoma of the left ureter on 22 May 2019. She underwent a left nephroureterectomy and received five cycles of chemoradiotherapy with cisplatin and gemcitabine from 31 May 2019 to 23 August 2019. However, she had a poor response to therapy. Therefore, she started receiving a pembrolizumab infusion 200mg every three weeks on 24 September 2019. Sixteen days after the first infusion of pembrolizumab (11 October 2019), she was admitted to the neurology clinic because of acute onset of bilateral ptosis. Her neurological examination showed complete bilateral ptosis (right ptosis developed one day before left ptosis) with no noticeable diurnal change. Her extraocular muscle movement (EOM) revealed all-direction limitation with mild and vertical adduction sparing. She had reactive symmetric pupil reflex with no diplopia, chemosis of the conjunctiva, orbital pain, proptosis, muscle pain, dyspnoea or facial numbness. No extremity, bulbar or axial involvement was noted. Laboratory examination revealed elevated levels of liver enzymes and creatine phosphokinase. On admission, her ESR and thyroid functions were normal, while autoimmune antibodies showed negative results for anti-muscle-specific kinase antibodies, anti-striated muscle and anti-acetylcholine receptors. The Gadoliniumenhanced MRI showed no signs of infection, inflammatory or mass lesions. The CSF analysis, repetitive stimulation test, ice pack test and CT scan of the mediastinum and chest were unremarkable. Based on findings, she was diagnosed with grade III pembrolizumab-induced myasthenia gravis-like disorder, ocular myositis and hepatitis. Hence, the woman received treatment with pyridostigmine 120mg daily for myasthenia gravis; however, the treatment was ineffective. Therefore, she started receiving methylprednisolone pulse therapy, which resulted in improvement of EOM and ptosis. Her liver enzymes also returned to baseline level. On 21 October 2019, she was discharged from the hospital with prednisolone. Due to the development of myasthenia gravis-like disorder, ocular myositis and hepatitis, her therapy with pembrolizumab was stopped, and she was lost to follow-up. After three months, she was readmitted due to the progression of urothelial cancer. Following careful consideration, the woman’s therapy with pembrolizumab re-started on 27 February 2020, along with prednisolone. Two weeks after administration of the second infusion of pembrolizumab, no complications (EOM limitation, neuroinflammatory symptoms or ptosis) were observed.