Pembrolizumab-induced agranulocytosis

Introduction: With the widespread use of anti-programmed death-1 monoclonal antibodies, such as pembrolizumab, rare side effects appear in clinical practice.

Case report: We report the case of a man diagnosed with non-keratinizing squamous lung carcinoma stage IVB with programmed death-ligand 1 70% who developed agranulocytosis 10 days after a single dose of pembrolizumab as monotherapy.

Management and outcome: Pembrolizumab was discontinued immediately. Grade 4 neutrophil decrease is mentioned in the product information sheet as a rare side effect. The patient was admitted in poor physical condition with grade 4 neutropenic fever, mucositis and anemia. Agranulocytosis did not improve despite treatment with granulocyte colony-stimulating factor, intravenous corticosteroids and intravenous immunoglobulins. He experienced a rapid worsening and died 3 weeks after admission. The causal relationship between pembrolizumab and the appearance of agranulocytosis was determined as possible according to Naranjo's modified Karch and Lasagna's imputability algorithm.

Discussion: Hematologic immune-related adverse events are uncommon but important side effects among patients treated with immune checkpoint inhibitors. Agranulocytosis and neutropenia are infrequently reported but can be life-threatening. The main approach for agranulocytosis consists of intravenous corticosteroids, granulocyte colony-stimulating factors and blood products. Depending on bone marrow characteristics, treatments for refractory patients include intravenous immunoglobulins or cyclosporine. After an immune-related adverse event, benefits and risks must be considered before continuation with an immune checkpoint inhibitor. Detection and communication of adverse drug reactions to the Pharmacovigilance Systems have special relevance for rare side effects.