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.