353: CYTOKINE RELEASE STORM FOLLOWING IMMUNE CHECKPOINT INHIBITOR USE MANAGED WITH TOCILIZUMAB IN THE ICU

Abstract

Introduction: Immune check point inhibitors (ICIs) have increased greatly in use as oncologic therapies continue to advance. Much is known regarding the inflammatory side effects of ICIs, but in the ICU it is often difficult to distinguish infection from an inflammatory response, or in rare situations cytokine release storm (CRS). We will discuss a case of CRS following ICI use in a critically ill patient treated with Tocilizumab to manage inflammation and neurotoxicity. Description: A 69 year old man with metastatic melanoma, treated with the ICI combination Ipilimumab and Nivolumab, with reduction in tumor burden presented with acute encephalopathy and seizures. The patient was febrile, hypotensive, and tachycardic. A lumbar puncture was performed showing a mild neutrophilic pleocytosis and signs of acute inflammation on cytology. Imaging as well as blood, urine, and CSF cultures failed to show a source of infection or increased tumor burden, but symptoms persisted. The negative infectious workup and markedly elevated inflammatory markers with CRP 16, WSR 86, and LDH 1,887 raised concern for a ICI mediated systemic inflammatory process, such as CRS. Pulse dose steroids were started, and mentation improved. However, fevers and tachycardia persisted. Tocilizumab was given for anti-IL 6 properties after IL-6 resulted at 34 (nl < 6). Following the initial dose, the fever curve broke and the CRP normalized. After the initial Tocilizumab dose the patient defervesced and inflammatory markers normalized. Recurrent spikes in fever and inflammatory markers resolved with repeated dosing on days 10 and 21 following the initial dose. Inflammatory markers improved and the patient was able to be transitioned from the ICU to continue his care under the oncology team. Discussion: ICIs have revolutionized care and achieve durable response in many cancers. They are associated with a wide spectrum of immune mediated toxicities, which can be difficult to distinguish from sepsis and can be life threatening if not recognized and treated. CRS and neurotoxicity are unusual and highlight the complexity of these toxicities and the need f to diagnose and treat early and aggressively. ICIs are now standard of care; therefore it is imperative for intensivists to become familiar with presentation and treatment of side effects.