SERIO is a registry for adverse events of immunotherapies (immune-related adverse events, irAE).
In particular, we aim to collect cases of rare, complex and therapy-refractory adverse events as well as adverse events in special patient groups (i.e. patients with autoimmune diseases or patients with a solid organ transplant). Immunotherapies include checkpoint-inhibitors, cellular therapies, e.g. CAR T cells, and bispecific antibodies.
Our goal is to improve side effect management, gain insights into the pathogenesis of irAE, and be able to make predictions about irAE.
Who we are
SERIO is based at the Department of Dermatooncology at the University Hospital of Munich (LMU). The SERIO online register is operated in cooperation with the Paul Ehrlich Institute. Over the past 13 years, we have collected more than 1832 cases of rare, complex or very severe side effects from 27 centres in 6 countries. We cooperate with side effect specialists from all over the world.
SERIO was first initiated in 2011 by dermatooncologists from the University Hospital of Erlangen. The first documented case of SERIO dates back to 2009. A close collaboration with endocrinologists, cardiologists and gastroenterologists soon developed, which led to the initiation of our interdisciplinary Tox Board. Our cooperation with the Working Group Dermatooncolgy (ADO) includes the implementation of joint projects and the exchange of experiences.
SERIO aims to help physicians manage side effects and gain better knowledge of side effects induced by immunotherapy.
What we do
- Collect and analyze cases of rare, complex, severe and therapy-refractory adverse reactions induced by immunotherapy
- Provide physicians with recommendations for the management of irAE
- Conduct research and assist others conducting research related to irAE
Case of the Month
Case of the month
04/22 nodular melanoma
pT4b pN3c M1b, St. IV (AJCC 2017)
04/2022 tumor resection (R1) and axillary lymph node dissection
06-08/2022 monotherapy with nivolumab
06/2022 tumor resection (R0)
08-09/2022 2 cycles of combined immunotherapy with ipilimumab 3mg/kg + nivolumab 1mg/kg (stopped)
Since 12/2022 BRAF/ MEK inhibitor therapy with BRAFTOFI (Encorafenib) + MEKTOVI (Binimetinib)
After 2 doses of combined immunotherapy with ipilimumab and nivolumab, the patient presented with immune-related hepatitis (irHepatitis), immune-related hypophysitis (irHypophysitis) and immune-related myocarditis (irMyocarditis). Subsequently prednisolone treatment was initiated. Due to the high dose corticosteroid therapy, the patient developed steroid-related diabetes mellitus.
In further laboratory tests to exclude other conditions, we report a newly discovered serum reactivity to purkinje cell cytoplasmic antibodies without anti-Yo specifity. Control analyses were performed to rule out a panel of previously described paraneoplastic antibodies known to be associated with paraneoplastic cerebellar degeneration. The patient presented without any neurological symptoms. Cranial MRI was normal.
As corticosteroid therapy improved symptoms of irMyocarditis and irHepatitis, prednisolone was tapered. For irHypophysitis treatment, hormone replacement therapy was continued with hydrocortisone. BRAF/ MEK inhibitor therapy was initiated.
We initiated a systemic therapy with prednisolone with an initial dose of 80mg/day and then tapered.
Hypophysitis treatment usually involves lifelong hormone replacement therapy. Hydrocortisone with a dose of 30mg/day was substituted. Due to the risk of acute adrenal crisis, patients needs to be educated to increase the dose in stress situations (infections, trauma etc.) and should carry an emergency card with them at all times.
If a patient has a positive test for purkinje cell cytoplasmic antibodies, a follow-up with FDG-PET/CT to identify any underlying lesion is advised. Further neurological assessments are planned.
The immunotherapy was permanently discontinued due to the risk of irMyocarditis, irHypophysitis and irHepatitis. Positive tests for purkinje cell cytoplasmic antibodies often appear to be unrelated to the development of neurological diseases, therefore interruption of immunotherapy may not be required.
Paraneoplastic cerebellar degeneration is an uncommon disorder that can be associated with different types of cancer. The most commonly associated cancers are small cell lung cancer, gynecologic cancer and lymphoma. Purkinje cell cytoplasmic antibody type 1 with anti-Yo specifity (PCA-1) predominantly associate with cerebellar degeneration (Wolters Kluwer et al., Uptodate, 2023).
But, a positive test for paraneoplastic antibodies, as the purkinje cell cytoplasmic antibody, does not indicate the presence or development of a neurological disease. Many patients can have a positive test at low titers. Even when detected at high titer, neurological symptoms or physical findings are not mandatory (Wolters Kluwer et al., Uptodate, 2023). To identify first signs of a neurological disorder, regular physical examinations are advised. FDG-PET/CT should be performed once to rule out cerebellar degeneration. MRI scans are often unremarkable.
Case reports reported of ipilimumab induced cerebellar degeneration in lung cancer patients (Hardwick et al., Neuropathology and Applied Neurobiology, 2021). Purkinje cell cytoplasmic antibody type 1 with anti-Yo specifity (PCA-1) tests were detected at low titer. Symptoms included severe ataxia, dysarthria, dizziness and double vision. Methylprednisolone and infliximab were initiated to improve symptoms.
Generally, treating the underlying cancer is the best way to control a paraneoplastic cerebellar degeneration (Elsevier, ScienceDirect, 2023).
A positive test for paraneoplastic antibodies is a very rare side effect of immune checkpoint inhibitors. Further research is now needed to evaluate the exact role of purkinje cell cytoplasmic antibodies without anti-Yo specifity. Neurological monitoring has to be indicated to detect changes in the clinical status of tumor patients.