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 patient groups (i.e. with autoimmune disease or solid organ transplant).
Who we are
SERIO was originally initiated by dermatooncologists at the University Hospital of Erlangen in 2011, a certified cancer center and home to the German center of Immunotherapy (DZI). The first documented case of SERIO dates back to 2009. There was soon a close 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.
As of this moment, SERIO is based at the Department of Dermatooncology at the University Hospital of Munich (LMU). We now host an online register in cooperation with the Paul-Ehrlich Institute. Over the course of the last 13 years, we were able to collect more than 1832 cases of rare, complex or very severe side effects from 27 centres in 6 countries. We are cooperating with side effect specialists from all over the world and are hoping 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 to physicians for the management of irAE
- Conduct research and support other people conducting research with regard to irAE
Case of the Month
Anti-PD-1 rechallenge after irHepatitis grade 3 and irPneumonitis grade 1 during combined anti-CTLA-4 / anti-PD-1 immunotherapy
- 05/2021 acrolentiginous melanoma of the left foot
- Initial stage: T4bN3bM1b, IV (AJCC 2017), BRAF wild-type
- Inguinal and iliac lymph node metastases
- One metastasis in small pelvis
- 06/2021 – 08/2021: Combination immunotherapy with ipilimumab (3 mg/kg bw) and nivolumab (1 mg/kg bw) every three weeks
- 08/2021 – 11/2021: Interruption of immunotherapy due to irPneumonitis grade 1 and irHepatitis grade 3
- 11/2021 – 01/2022: Nivolumab 240 mg every two weeks
After 4 doses of combination immunotherapy with ipilimumab and nivolumab, a chest CT performed for staging showed a nonspecific interstitial pneumonia (NSIP)-pattern. The patient was completely asymptomatic (no dyspnoea, malaise, cough or fever). We diagnosed irPneumonitis grade 1 (CTCAE). In the follow-up laboratory check, AST and ALT were elevated > 5 x ULN. Therefore, in addition irHepatitis grade 3 (CTCAE) was diagnosed.
The immunotherapy was interrupted. Therapy with methylprednisolone 1.5 mg/kg bw for three days was initiated and tapered over the following weeks. The transaminases declined and the pulmonary radiological findings clearly improved. The patient remained asymptomatic at all times.
After normalization of transaminases, we reinitiated monotherapy with nivolumab 240 mg every two weeks. To date, the patient has received five doses of nivolumab and has remained asymptomatic. The transaminases remained within the normal range.
A rechallenge with immunotherapy carries the risk of reexacerbation of the irAE but may be indicated in certain circumstances.
Pollack et al. studied 80 patients who had to interrupt combined immunotherapy due to an irAE. Of those patients 39% experienced recurrent (18%) or clinically significant distinct (21%) irAE with anti-PD-1 monotherapy resumption. In this study, recurrence of irAE was independent of the duration of steroid taper, use of other immunosuppressants in addition to steroids, and the severity of the initial irAE. Under rechallenge with anti-PD1 monotherapy, a complete or partial response was observed in 70% of the patients, a stable disease in 19% and a progressive disease in 11% (Pollack et al, Ann Oncol., 2018).
Patients who are rechallenged show a reexacerbation in about a third of the cases if challenged with the same immunotherapy (Abu Seibh et al, J Clin Oncol., 2019) and 18% if challenged with monotherapy after combination immunotherapy. Thus, a rechallenge with immunotherapy can be considered in side effects that are not live-threatening, as there is a high probability of good efficacy. Patients have to be informed about the risk of reexacerbation. Clinicians should use critical judgement and extreme caution in resuming immunotherapy in patients with life threatening irAE such as myocarditis.
In our case, the rechallenge with nivolumab has been well tolerated so far.