- cutaneous melanoma, St. IV (AJCC 2017)
- progredient lymph node- and skin metastases
- BRAF wildtype
- FBXW7 mutation
- pre-exisiting autoimmune disease: neuromyelitis optica
- epifocal administration of dinitrochlorobenzene (DNCB) combined with systemic chemotherapy with dacarbazine (DTIC); progressive disease
- therapy with sorafenib; progressive disease
- immunotherapy with ipilimumab (2 cycle); progressive disease and death
Shortly after initiation of the immunotherapy (IT) with pembrolizumab the patient presented with acute paraplegia and urinary retention due to transverse myelitis.
We discontinued the immunotherapy due to severe adverse event (CTCAE Grade 4). Although immmunosuppressive therapy was initiated immediately the patient died six months later.
In the past most patients with preexisiting autoimmune diseases have been excluded from clinical trials evaluating checkpoint inhibitors because of a possible exazerbation of the underlying disease. Interestingly, retrospective studies show that less than 50% experienced flares which were often mild and easily managed by immunosuppressive therapy (Gutzmer et al., Eur. J. Cancer. 2016). Nevertheless, they can be severe and potentially fatal as seen in our example. Severe side effects are especially described in preexisiting neurological autoimmune diseases (Safa et al., J. Immunother. Cancer. 2019). Further investigation is needed to understand the mechanisms of autoimmunity in the context of immunotherapy-induced side effects to evaluate the individual risk of patients before starting an immunotherapy.
