SERIO is a registry for adverse events of immunotherapies (immune-related adverse events, irAE): The aim of SERIO is to collect rare, complex and therapy-refractory cases to obtain knowledge for better side effect management and eventually be able to understand pathogenesis and predict side effects also in special patients (i.e. with autoimmune disease or solid organ transplant).
Case of the Month
79 year old patient with checkpoint-inhibitor induced myositis and myasthenia gravis overlap syndrome
- 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.
Who we are
SERIO was originally initiated by dermatooncologists at the University Hospital of Erlangen in 2011 with the first documented case dating back to 2009. We are a certified cancer center and home to the German center of Immunotherapy (DZI). There was soon an intensive collaboration with endocrinologists, cardiologists and gastroenterologists that led to our interdisciplinary tox-board. We have also continuously collaborated within the Working Group Dermatooncolgy (ADO) to conduct projects, share experiences and gain new insights. More than 1000 cases of rare complex or very severe side effects from five countries were collected in a period of almost 10 years. We now host an online register in cooperation with the Paul-Ehrlich Institute. Today, we are cooperating with side effect specialists all over the world and hope to improve side effect management for cancer patients.
SERIO is there to help physicians manage side effects and obtain better knowledge on side effects induced by immunotherapy.
What we do
- Collect and analyze cases of rare, complex, severe and therapy-refractory side effects induced by immunotherapy
- Give recommendations for treating physicians confronted with difficult irAE
- Conduct research and support for people conducting research with regard to irAE