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
46-year old patient with prolonged irHepatitis and thrombopenia
- 04/2007 SNB (0/3)
- 07/2007 – 07/2009 Interferon-alpha 3x3 Mio IE s.c./week
- 11/2018 -11/2019 Immunotherapy with ipilimumab/pembrolizumab (4 cycles), followed by pembrolizumab
- 11/2019-12/2019 BRAF/MEK inihibitior therapy with dabrafenib/trametinib
- 12/2019-02/2020 BRAF/MEK inihibitior therapy with encorafenib/binimetinib
3 months after initiation of the immunotherapy (IT) the patient experienced a hypophysitis that was substituted with hydrocortisone. 5 months after initiation she presented with an irGastritis with a concomittant Addison crisis. Subsequently she had progressive disease and was switched to dabrafenib/trametinib. 12 months after start of IT and one month after start of BRAF/MEK inihibitor therapy she presented with sinus bradycardia, pyrexia and again Addison crisis. Dabrafenib/trametinib was replaced by encorafenib/binimetinib. Another 3 months later she developed CTCAE grade 3 irHepatitis with histological confirmation. Prednisolone was initiated at 1 mg/kg body weight and transaminases decreased. However, on tapering they increase up to 1987 U/l ALT and 1496 U/l AST. Bilirubin was measured up to 21,6 mg/dl.
Prednisiolone was increased to 1000 mg/day, mycophenolate mofetil (MMF 500 mg 1-0-1) and infliximab were added. Supportive drugs included rifampicin 150 mg (1-0-0) and konakion.
Since she was progressive under immunotherapy no attempt to rechallenge was undertaken. After recovery of irHepatitis BRAF/MEK Inhibitor therapy with vemurafenib/cobimetinib was induced.
In general, irHepatitis is common (7-33%) and can be fatal. Thrombopenia is rare (1.2-4.7%) and can mostly be well-managed. Sequential therapy with immunotherapy and subsequent BRAF/MEK Inhibitor theapy may lead to new complex side effect profiles (Dimitriou et al. J Immunother, 2018) as in this patient with sinus bradycardia that could not clearly be attributed to any specific drug. Escalation of immunosuppresion with MMF and infliximab worked well to treat irHepatitis in this patient.
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