Cytokine Release Syndrome During Sequential Treatment With Immune Checkpoint Inhibitors and Kinase Inhibitors for Metastatic Melanoma

• Published in: Journal of immunotherapy (1997) Vol. 42; no. 1; p. 29
• Main Authors: Dimitriou, Florentia, Matter, Alexandra V, Mangana, Joanna, Urosevic-Maiwald, Mirjana, Micaletto, Sara, Braun, Ralph P, French, Lars E, Dummer, Reinhard
• Format: Journal Article
• Language: English
• Published: United States 01.01.2019
• Subjects: Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Biomarkers; Biopsy; Cytokine Release Syndrome - diagnosis; Cytokine Release Syndrome - etiology; Female; Humans; Melanoma - complications; Melanoma - drug therapy; Melanoma - etiology; Melanoma - pathology; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins B-raf - genetics
• ISSN: 1537-4513
• DOI: 10.1097/CJI.0000000000000236

Switching from immunotherapy to targeted therapy in metastasized melanoma can be complicated by a cytokine release syndrome (CRS). CRS is a serious complication, which is induced by high levels of circulating cytokines, associated with T-cell engagement and proliferation, and results in a constellation of symptoms with variable organ involvement. We report 2 patients with BRAF V600 mutant melanoma who were previously treated with anti-PD-1±anti-LAG-3 antibodies and were switched to BRAF/MEK-inhibitors because of progressive disease. Both cases depict the complexity of interactions occurring during sequential treatment with immune checkpoint inhibitors and kinase inhibitors. Early identification and management of CRS is crucial to decrease its toxicity and improve safety of further drugs to be given in a therapeutic ladder.