1. INTRODUCTION
Immunotherapy with T-cells genetically engineered to express CD19-specific chimeric antigen receptor (CAR) has dramatically changed the treatment of aggressive B-cell malignancies1,2. Two products- Tisagenlecleucel and Axicabtagene ciloleucel- have been approved by the European Medicines Agency (EMA) for the treatment of relapsed/refractory CD19+ diseases. Tisagenlecleucel (Tisa-Cel) is a CD19-targeted CAR-T cell therapy approved to treat adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy and children and adults up to age 25 with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)3,4.
Despite CAR-T cells can induce rapid and durable responses, this therapy is associated to specific and severe toxicities, representing an obstacle in its widespread use. Cytokine-release syndrome (CRS) is the most frequent toxicity after infusion5,6. This systemic inflammatory response can rarely evolve into a fulminant hemophagocytic lymphohistiocytosis/macrophage-activation syndrome (HLH/MAS) which is associated with high mortality rates7,8. Diagnosis criteria for this entity have been recently proposed7, but discrimination between severe CRS, CAR-T related HLH/MAS and malignancy-associated HLH/MAS can be challenging.
We describe two cases of CAR-T cell related HLH/MAS and the difficulties linked to the diagnosis and management of this unusual complication.