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). 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
61-year-old patient with steroid-refractory irColitis and 2nd line therapy with infliximab, vedolizumab (α₄β₇ integrin blocker) and extracorporeal photopheresis (ECP)
- 04/2021 melanoma of unknown primary (MUP)
- Initial stage: pTxNxM1d(0), IV (AJCC 2017), BRAF wild-type
- Cerebral metastases
- 06/2021: Stereotactic radiosurgery of cerebral metastases
- 06/2021: Combination immunotherapy with ipilimumab 3 mg/kg bw and nivolumab 1 mg/kg bw, every three weeks
- 09/2021: Stereotactic radiosurgery of cerebral metastases
- 09/2021: Chemotherapy with temozolomide 200 mg/m²
- 10/2021: Re-Immunotherapy with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw (flip dose), every three weeks
- 10/2021: Stereotactic radiosurgery of cerebral metastases
- 01/2022: Chemotherapy with gemcitabine 1000 mg/m² and treosulfan 3500 mg/m²
After one dose of ipilimumab + nivolumab, irHepatitis grade 1 (CTCAE) and irColitis grade 1 (CTCAE) occurred. The immunotherapy was interrupted. Initial therapy:
- Methylprednisolone 1 mg/kg bw
During an attempt to taper off the steroids, irColitis grade 2 (CTCAE) developed with diarrhea up to 7 times per day. Therapy:
- Methylprednisolone 1.5 mg/kg bw
- Infliximab 5 mg/kg bw i.v.
After this therapy, the patient was initially symptom-free. But when the steroids were tapered off, there was a recurrence of irColitis (grade 2) on 10 mg prednisolone. The patient had to be admitted to the hospital. Therapy:
- Methylprednisolone 1 mg/kg bw
- 2nd Dose of infliximab 5 mg/kg bw i.v.
- Start of extracorporeal photopheresis (ECP)
Initially, there was a further deterioration of the irColitis. The patient developed severe diarrhea, some with blood, fecal incontinence and dehydration (irColitis grade 4). Therapy:
- Methylprednisolone 2 mg/kg bw
- Continuation of extracorporeal photopheresis (weekly)
- Vedolizumab 300 mg i.v.
With this therapy, the symptoms improved over time. A second dose of vedolizumab was administered. The intervals of the ECP could be extended to every 2 weeks. Due to cerebral progress, stereotactic radiosurgery was repeated and chemotherapy with temozolomide 200 mg/m² was initiated.
Due to renewed significant cerebral tumor progression, the decision was made to reinitiate a combined immunotherapy with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw (flip dose), every three weeks after a risk-benefit assessment and thorough patient information. Stereotactic radiosurgery was performed again. Unfortunately, the colitis symptoms returned. Tumor therapy was switched to chemotherapy with gemcitabine and treosulfan.
For the treatment of steroid-refractory irColitis, most guidelines recommend therapy with infliximab as the first step for patients who do not show any improvement within 3-5 days with steroids (Thompson et. al, J Natl Compr Canc Netw., 2020; Brahmer et. al., J Clin Oncol., 2018).
The integrin antagonist vedolizumab may be considered in infliximab-refractory irColitis according to ESMO-, NCCN- and ASCO guidelines for the management of immune-related adverse events. In a study from 2017, vedolizumab relieved symptoms in 6 of 7 patients with steroid-dependent or steroid-refractory irColitis; no side effects were reported (Bergqvist et. al., Cancer Immunol Immunother., 2017).
ECP consists of the three steps of leukapheresis, photoactivation and reinfusion and has immunomodulatory effects (modulation of dendritic cells, change in cytokine profile, induction of T cell subpopulations). Indications are currently the treatment of Sézary syndrome, Graft-versus-host disease (GvHD), organ transplant rejection and systemic scleroderma. Importantly, there is no attenuation of the anti-tumor response as far as reported from lymphoma patients in contrast to potential effects of immunosuppression with drugs. Apostoleva et. al. reported on a case of a 29-year-old patient with steroid-refractory irColitis who showed only slight improvement or recurrence after administration of infliximab and ciclosporin, and in whom combined drug therapy with ECP was able to achieve freedom from symptoms and recurrence (N Eng J Med., 2020). This indicates that an off-label use of ECP for the treatment of irAE is possible and promising.