- 01/2021 Nodular malignant melanoma left knee
- 06/2022: lymph node metastasis left inguinal, complete resection
- pT2aN1bM0, IIIB (AJCC 2017)
- 07/2022 Adjuvant immunotherapy with pembrolizumab
After 2 doses of adjuvant immunotherapy with the immune checkpoint inhibitor pembrolizumab, the patient presented with bilateral hearing loss. Furthermore, they developed dyspnea and leg edema. Troponin and nt-pro-BNP were slightly elevated. The D-dimer was slightly elevated and the ECG showed an S1Q3 type, thus we ruled out a pulmonary artery embolism using CT angiography. Echocardiography showed preserved systolic function and diastolic dysfunction (HFpEF, heart failure with preserved ejection fraction). A cardiac catheter examination could rule out a stenosis requiring intervention.
A cardiac MRI showed focal transmural late gadolinium enhancement (LGE) of the basal inferior wall. Since, in addition to inflammatory changes, cardiac metastases were also part of the differential diagnosis, a PET-CT was performed for further clarification. Finally, we agreed on ICI-myocarditis as the most likely cause. A myocardial biopsy was not performed due to the difficult localization.
We initiated systemic therapy with prednisolone with an initial dose of 1000 mg, which was reduced to 1 mg/kg after 5 days and then tapered. A weight reduction of 4 kg could be achieved through a negative fluid balance. A follow-up cardiac MRI is planned.
The immunotherapy was permanently discontinued.
Myocarditis is a rare side effect of immunotherapy (incidence ca. 1%) with a very high mortality (50%), therefore cardiac biomarkers should be regularly monitored during immunotherapy. Before starting therapy, a baseline ECG and troponin determination should be performed. Biomarker abnormalities or clinical symptoms should be followed by cardiac evaluation. Troponin and ECG taken together are abnormal in 50-90% of cases of ICI-myocarditis, cardiac MRI shows changes in 25-50% of cases. Echocardiography is often unremarkable. A cardiac catheter examination should be performed once to rule out coronary artery disease; myocardial biopsy is gold standard. Immunotherapy should be interrupted or discontinued and systemic corticosteroid therapy (1-2 mg/kg or even 1g/day) initiated. In therapy-refractory cases, mycophenolate mofetil (MMF), infliximab or anti-thymocyte-globuline (ATG) have been suggested as second-line therapies (ASCO-Guidelines, Schneider BJ, J Clin Oncol, 2021). Case reports reported on the successful use of abatacept and alemtuzumab as second-line therapies for ICI-myocarditis (Salem JE, N Engl J Med, 2019; Esfahani K, N Engl J Med, 2019).
Myocarditis is a rare side effect of immune checkpoint inhibitors with extremely high mortality, therefore monitoring of cardiac biomarkers and good side effect management is crucial.
