- 09/2020: cutaneous melanoma of the back (Breslow tumor thickness 4 mm)
- initial stage: pT3a N1a M0, IIIA (AJCC 2017), BRAF wild-type, NRAS wild-type
- pre-existing diseases: three-vessel coronary artery disease, myocardial infarction (05/2020)
- 10/2020: re-excision within a safety margin of 2 cm and positive sentinel lymph node biopsy
- 10/2020: start of adjuvant immunotherapy with pembrolizumab 200 mg q3w (1 cycle)
Three weeks after initiation of the immunotherapy with pembrolizumab the patient presented to the emergency room with double vision, decreased muscle strength as well as slurred speech, dysphagia and dropped head syndrome. Laboratory results showed an elevated creatinine kinase (CK) of 4500 U/l as well as positive AChR- and Titin antibodies. Furthermore, irHepatitis (CTCAE grade III) was detected. Muscle sonography and electromyography were typical for an overlap of irMyasthenia gravis and irMyositis.
Therapy with methylprednisolone (1 g/d) was initiated for five days and was tapered in the following weeks. Furthermore, immunoglobulins (2g/kg bodyweight) were substituted for three days. CK and liver enzymes decreased under the immunosuppressive therapy and the patient slowly improved.
Approximately seven weeks after initiation of the immunotherapy and while being on prednisolone 70 mg/kg bodyweight the patient presented again to the emergency room due to a sudden deterioration of the general condition, two syncopes at night as well as flank pain and nausea. Urological work up was without pathological findings and a CT scan of the abdomen didn`t show any abnormalities. During further clinical work up, the patient suddenly lost consciousness due to asystolia. Subsequently, resuscitation was performed. Unfortunately the patient died; the cause of death remains unclear. A possible cardiac involvement of myositis was discussed but could not be confirmed due to refused autopsy by the family.
Immunotherapy was stopped due to severe immune-related adverse event (CTCAE grade IV).
Myopathies are frequently reported neurological side effects. Myositis can be accompanied by myocarditis and is associated with a high mortality rate (Knauss et al., der Nervenarzt, 2018).
Since often oligosymptomatic diagnosis can be delayed. Rapid initiation of immunosuppressive treatment is essential for better outcomes.
Myasthenic syndromes under immunotherapy mainly appear with bilateral ptosis, dysphagia and weakness of several muscle groups, as shown in our patient. Most frequently they manifest as a new-onset myasthenia, but exacerbation of preexisting disorders have been observed (Roth et al., Cancer Treatment Reviews, 2021).
Many questions remain unclear regarding immune-related neurological complications like risk factors, biomarkers for monitoring, and best options for second-line immunosuppressants in steroid refractory patients.
Controlled studies on the treatment of neurological side effects are important to improve outcome of these patients and to avoid long-term sequelae.
