(469) Immune Checkpoint Inhibitor-Induced Fatal Hemophagocytic Lymphohistiocytosis

Introduction: The increasing use of immune checkpoint inhibitors (ICI) for the treatment of various cancers has also unraveled a spectrum of immune-related adverse events (irAEs). Acquired or secondary hemophagocytic lymphohistiocytosis (sHLH), is a rarely described irAE. In sHLH, uncontrolled activation of immune cells results in a hyperinflammatory, life-threatening “cytokine storm” that can progress to multi-organ failure and necessitate intensive care unit (ICU) management.

Description: A 64-year-old man with recently diagnosed metastatic prostate cancer presented to the hospital after several days of high fevers. He had received his first dose of atezolizumab, a programmed death-ligand 1 antibody, 2 weeks prior in addition to androgen-blocking therapy. Admission blood work was notable for transaminitis, leukopenia, and thrombocytopenia. Computed tomography scan of the chest, abdomen and pelvis showed hepatosplenomegaly. Over the next 24 hours, the patient developed hypoxia requiring transfer to the ICU and ultimately intubation and mechanical ventilation. A cytokine panel revealed elevated levels of tumor necrosis factor-α (85 pg / mL), interleukin 10 (639 pg / mL), and interleukin 6 (156 pg / mL) levels. The soluble interleukin-2 receptor level surpassed the upper threshold of detection (20,000 pg / mL), while serum ferritin was extremely elevated at 216,746 ng / mL. The patient rapidly developed worsening transaminitis, coagulopathy, pancytopenia, kidney injury with metabolic acidosis, and shock requiring multiple vasopressors. On suspicion of sHLH, intravenous tocilizumab and pulse-dosed methylprednisolone were administered, but the patient expired within hours.

Discussion: We describe a rapidly progressive and fatal case of sHLH within two weeks of receiving atezolizumab. A recent review found that the majority of sHLH cases occurred after pembrolizumab or ipilimumab-nivolumab combination regimens, with most having a favorable outcome following treatment with corticosteroids alone. To our knowledge, our case represents the second reported instance of sHLH in a patient receiving atezolizumab, with the first case also resulting in the patient’s death.