• Metastatic cutaneous melanoma, AJCC stage IV (pT4 N0 M1b)
• BRAF: Wildtype
• Pulmonary metastases

• 08/2017: Excision Melanoma left forearm, pT4 N0 M0 – AJCC Stage IIC
• 05/2020: Multiple pulmonary metastases, pT4 N0 M1b – AJCC Stage IV
• 05/2020: Start Nivolumab 240 mg i.v. (no combination therapy with Ipilimumab+Nivolumab because of advanced age), discontinued due to immune-related Multi-Toxicity
• 06/2025: Staging: Minor progression of a pulmonary nodule, no clinically relevant tumor progression

The patient developed multiple ICI-associated toxicities (irAdrenalitis treated with hydrocortisone, irPsoriasis treated with apremilast, right gonarthritis treated with intra-articular steroid, short systemic steroid courses and  MTX – MTX stopped in 04/2024). In 11/2024 an asymptomatic troponin rise and cardiac MRI findings (diffuse myocardial edema, subtle non-ischaemic Late Gadolinium Enhancement, preserved Ejection fraction) were suspicious for irMyocarditis.

The cardiologic department recommended stopping nivolumab and close monitoring. Nivolumab was discontinued (11/2024) and the course was conservative with serial troponin and cardiac MRIs: In 06/2025 the cardiac MRI still shows persistent edema but the patient is asymptomatic and troponin is only slightly elevated (0.02 ng/ml). At the interdisciplinary ToxBoard (07/2025) escalation to high-dose systemic steroids was advised because of the persistent myocarditis activity.

Currently, re-challenge with ICI is not recommended in the setting of myocarditis and multiple other severe irAEs. It is possible in highly selected cases after resolution of irAEs, extensive multidisciplinary risk–benefit assessment and informed consent.

Multi-toxicity refers to the simultaneous or sequential occurrence of irAEs across multiple organ systems. It is particularly common with combined ipilimumab + nivolumab therapy, occurring in up to 40% of patients. Management is especially challenging because the ideal approach treats all active irAEs without impairing antitumor efficacy by using multiple second-line immunosuppressive agents.

Discontinuation of nivolumab was appropriate given cardiac involvement and prior multi-organ irAEs and stable tumor disease; continue close monitoring and treat with high-dose steroids because of persistent myocardial inflammation.

• ESMO Clinical Practice Guidelines — management of immunotherapy toxicities.
• ASCO guidelines / consensus statements on immune-related adverse events.
• Li, Y., G. Pond, and E. McWhirter, Multisystem Immune-Related Adverse Events from Dual-Agent Immunotherapy Use. Curr Oncol, 2024. 31(1): p. 425-435.