Methylprednisolone/pembrolizumab/prednisolone

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 71-year-old woman developed colitis and dermatomyositis during treatment with pembrolizumab for cancer of unknown primary origin. Additionally, she developed cataract and oral candidiasis, and exhibited lack of efficacy during treatment with methylprednisolone and prednisolone for dermatomyositis [routes and durations of treatments to reactions onsets not stated; not all dosage stated].

The woman was referred to the hospital in Japan due to high fever and difficulty walking after her sixth course of pembrolizumab. She had past medical history of appendectomy, kidney biopsy for chronic glomerulonephritis and ovarian cyst surgery. She was diagnosed with a cancer of unknown primary origin 16 months earlier based on the results of biopsy of the cervical lymph nodes. Subsequently, she received eight courses of carboplatin and paclitaxel. She had progressive disease. As the initial pathological immunostaining suggested primary lung adenocarcinoma as the origin, she started receiving pembrolizumab as the second line of chemotherapy. She had received first course of pembrolizumab 5 months prior to current presentation. After the second course of pembrolizumab, she had developed grade 2 pembrolizumab-induced colitis.

The woman had received treatment with prednisolone. Subsequently, the dose of prednisolone was tapered to 15 mg/day. After the fourth course, a contrast-enhanced CT scan revealed shrinkage of the lymph node metastasis. Three days after the administration of sixth course of pembrolizumab, she developed a high fever and difficulty walking and was admitted to the hospital in Japan (current presentation). She had a body temperature of 39.2°C, pulse of 92 beats/minute, blood pressure of 94/66mm Hg and oxygen saturation of 92% on room air. Physical examination detected heliotrope rash on eyelids, nonspecific erythema of the forehead and erythema of the chest (V-neck signs). Limb oedema was noted in all four limbs along with muscle weakness in both thighs. Laboratory evaluation showed increased C-reactive protein. Blood cultures were negative. Urinalysis revealed no abnormalities. She tested negative for SARS-CoV-2. She tested negative for antinuclear antibodies, anti-aminoacyl tRNA synthetase antibody, anticardiolipin antibody, anti-transcriptional intermediary factor 1-g antibodies and anti-acetylcholine receptor antibodies. Electrocardiogram was normal. Cardiac/abdominal echography revealed no remarkable abnormal findings. A chest CT revealed no complications of thymoma or interstitial pneumonia. A MRI of the thighs revealed signal abnormalities in the left lateral and distal vastus medialis muscle. Head and spine MRI revealed no evidence of metastatic tumours or other abnormalities. Given the absence of infectious aetiology and time of symptoms onsets, immune related adverse event (irAE) was suspected. The diagnosis of grade 3 pembrolizumab-induced dermatomyositis was made based on the abnormal signals in the left lateral and distal vastus medialis muscle, presence of a heliotrope rash and weakness of the quadriceps muscles. She started receiving methylprednisolone 125 mg/day for dermatomyositis after admission and continued for 3 days. Considering the possibility of sepsis she received levofloxacin. After three days, she started receiving prednisolone 40 mg/day. But fever flared to 38°C or more, and inflammatory findings worsened. Therefore, dermatomyositis was considered refractory to corticosteroid therapy (lack of efficacy). Meanwhile, she had developed steroid (methylprednisolone and prednisolone)-induced cataracts and oral candidiasis. Therefore, the dose of corticosteroids could not be increased. Owing to renal dysfunction and the risk of opportunistic infections due to immunosuppression, she was treated with immune globulin [immunoglobulin] for dermatomyositis. Subsequently, the weakness of the quadriceps improved. She was able to walk independently. The inflammatory parameters became negative. Dose of prednisolone was gradually reduced, without relapse of symptoms. Finally, she achieved remission and was discharged. After discharge, prednisolone was further tapered. No fare up of dermatomyositis symptoms was noted, and remission continued. No progression of cancer was noted over 6 months after pembrolizumab discontinuation [not all outcomes stated].