Stage IIIA KRAS/STK11/TP53-mutated lung adenocarcinoma: fatal pembrolizumab-induced myocarditis after adjuvant therapy

What happened, in summary

This 71-year-old man had a 70-pack-year smoking history and had previously undergone radical prostatectomy for prostate cancer. In May 2024, he underwent left upper lobectomy for Stage IIIA lung adenocarcinoma, pT2N2. The tumor had a Ki-67 index of 20-25%, PD-L1 expression of 10%, and mutations in KRAS exon 2, STK11, and TP53. After surgery, he received adjuvant cisplatin plus pemetrexed. Sixteen days before his emergency presentation, he received his first cycle of adjuvant pembrolizumab. He came to the hospital with 3 days of palpitations, severe weakness, fatigue, and exhaustion with minimal exertion, but no chest pain or shortness of breath. ECG showed sinus tachycardia and a new right bundle branch block. Troponin, CK, CK-MB, liver enzymes, inflammatory markers, and D-dimer were elevated. Coronary angiography ruled out obstructive coronary disease, CT pulmonary angiography ruled out pulmonary embolism, and infectious testing was negative. Cardiac MRI supported immune-checkpoint-inhibitor myocarditis. Treatment began with high-dose IV methylprednisolone plus cardiovascular medications. When troponin did not fall, mycophenolate mofetil was added. His condition worsened with conduction blocks, ventricular arrhythmias, biventricular dysfunction, and LVEF of 35%. He needed amiodarone, lidocaine, intubation, vasopressors, an intra-aortic balloon pump, abatacept, and later continuous hemofiltration for renal failure. He died from sepsis and multi-organ failure after 15 days of hospitalization. The myocarditis was considered pembrolizumab-related because it appeared soon after the first infusion, coronary disease and pulmonary embolism were excluded, and cardiac MRI showed diffuse myocardial inflammation rather than a single blocked-vessel pattern. This severe cardiac toxicity, not recurrent lung cancer, drove the final hospitalization.