Case

68-year old patient with hemorrhagic irGastritis

Patient medical history
1
Melanoma of the skin, stage IV M1d (AJCC 2017)
06/1998 Cutaneous melanoma, left lower leg, Breslow 0,9 mm
07/2005 Nodular melanoma, BRAF wildtype, left lower leg, Breslow 1,25 mm
05/2008 Subcutaneous metastases, left lower leg
10/2008 Nodular metastases
since 09/2009 Recurrent subcutaneous metastases, left thigh
02/2020 Cerebral metastasis
2
Oncological therapy
08/2005 SNB (1/3)
09/2005 Lymph node dissection
09/2008 Radiotherapy, left lower leg
07/2008 - 12/2008 Interferon-alphha 3x3 Mio IE s.c./week
01/2014 - 08/2014 Radiotherapy, inguinal left
Since 04/2009 Autologous vaccination with tumor-RNA loaded dendritic cells
06/2018 - 03/2020 Immunotherapy with pembrolizumab
03/2020 Cerebral radiotherapy
03/2020 Immunotherapy with ipilimumab/nivolumab (3 cycles)
Immune related adverse event

21 months after initiation of the immunotherapy (IT) and 3 months after switching to combinational IT the patient experienced a hypophysitis that was substituted with hydrocortisone. 1 month later she presented with severe nausea, weight loss and dysphagia. During the following hospitalisation a CTCAE grade 3 hemorrhagic irGastritis and a concomittant CTCAE grade 2 irHepatitis were diagnosed, both with histological confirmation.

How did we proceed?

Pantoprazol 40 mg twice a day was given and prednisolone was initiated at 1 mg/kg body weight and transaminases decreased. Due to steroidrefractory dysphagia and nausea, we planned a therapy with infiximab at 5 mg/kg body weight. Already 3 days after the infliximab-infusion the dysphagia improved and the nausea ceased.

Could we continue the immunotherapy?

We interrupted the immunotherapy and monitored the patient closely. We decided due to the severity of the immune related adverse event and the current stable disease to interrupt the treatment until the next staging. Afterwards we will discuss a rechallenge interdisciplinarily. 

Our conclusion

Gastrointestinal irAEs are common (22-48%) (Heinzerling, L. et al. Dtsch Arztebl Int. 2019). However, solitary upper gastrointestinal events have been rarely reported. In general, an early therapy with infliximab in steroidrefractory gastrointestinal irAEs showed a quicker resolution (Johnson DH et al. J Immunother Cancer 2018) and is recommended in patients with persisting symptoms after 3-5 days (Haanen JBAG et al. Ann Oncol 2017). Escalation of immunosuppression with infliximab worked well and rapidly to treat irGastritis in this patient.