Hemophagocytic Lymphohistiocytosis As an Immune-Related Adverse Events in a Patient with Advanced Lung Adenocarcinoma

Abstract

I ntroduction: Immune checkpoint inhibitors (ICIs) have been approved as single agents or in combination with cytotoxic chemotherapy for use in the treatment of different tumor types including skin, lung, kidney, endometrium, bladder..., especially in advanced stages. ICIs are usually well tolerated and despite their demonstrated clinical benefit, severe immune-related adverse events (irAEs) can sometimes occur, including colitis, hepatitis, myocarditis, glomerulonephritis, pneumonitis, hypophysitis... Here we are reporting a case of hemophagocytic lymphohistiocytosis (HLH), a rare but potentially life-threatening complication of ICI therapy. Case presentation: We present the case of a 60-year-old female with metastatic adenocarcinoma of left lung who presented to the emergency room with a week history of generalized weakness, worsening dyspnea on exertion and decreased appetite while on maintenance ICI with pembrolizumab for approximately 1 year. On admission vital signs were a blood pressure of 88/70mmhg, pulse rate of 139 beats per minute, respiratory rate of 20 cycles per minute, temperature of 98.3°F and oxygen saturation of 98% on room air. Physical exam was unremarkable. A complete blood count revealed leukopenia of 2.7k/uL, hemoglobin of 11.8 g/dL, and mild thrombocytopenia of 131k/uL. A basic metabolic panel was significant for hyponatremia of 133 mmol/L, blood urea nitrogen of 43mg/dL, and creatinine of 1.71mg/dL. She was started on empiric broad-spectrum antibiotics with IV vancomycin and cefepime due to concern for infection in the setting of recurrent febrile episodes and neutropenia. Worsening pancytopenia prompted further work-up and showed elevated ferritin of 19581, lactate dehydrogenase of 2380, folate > 20, vitamin B 12 of 1645, iron level of 62, elevated total and direct bilirubin of 6.3 and 2.9 mg/dL, haptoglobin < 10 mg/dL, fibrinogen level of 174, C- reactive protein of 73.9. Elevated soluble IL2- receptor elevated at 10336.7, d-dimer > 20, elevated partial thromboplastin time of 51.1, Prothrombin Time of 20.5, INR of 1.7. Peripheral blood smear was unremarkable. Hemophagocytic lymphohistiocytosis was suspected and a bone marrow was performed prior to initiation of intravenous steroids. Bone marrow showed evidence of abundant histiocytes with hemophagocytosis of nucleated cells. She was discharged on an oral steroid taper. She has since been well without evidence of tumor progression off therapy for over 2 years now. Discussion: HLH is a rare but potentially life-threatening complication of ICI therapy that requires prompt recognition and management. Our patient responded well to steroids and did not require cytotoxic chemotherapy with etoposide.