Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies.
Rita GodinhoAlessandra NotoCraig FenwickAthina StravodimouSarah HugelshoferSolange PetersRoger HullinMichel ObeidPublished in: Journal for immunotherapy of cancer (2023)
Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1β, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.
Keyphrases
- epidermal growth factor receptor
- induced apoptosis
- oxidative stress
- cell cycle arrest
- tyrosine kinase
- left ventricular
- dendritic cells
- nk cells
- case report
- magnetic resonance imaging
- early onset
- rheumatoid arthritis
- regulatory t cells
- endoplasmic reticulum stress
- endothelial cells
- signaling pathway
- mesenchymal stem cells
- magnetic resonance
- artificial intelligence
- newly diagnosed