Management of cytokine release syndrome and macrophage activation syndrome following CAR-T cell therapy: Guidelines from the SFGM-TC

The use of chimeric antigen receptor T cells (CAR-T) has increased since their approval in the treatment of several relapsed/refractory B cell malignancies. The management of their specific toxicities, such as cytokine release syndrome (CRS), tends to be better understood and well-defined. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on the management of patients developing CRS following CAR-T cell therapy. A special chapter has been allocated to macrophage activation syndrome (MAS), a rare but life-threaten-ing complication post-CAR-T. In addition to symptomatic measures and preemptive broad-spec-trum antibiotics, immunomodulators such as tocilizumab and corticosteroids remain the corner stone for the treatment of CRS. Tocilizumab/corticosteroids-resistant CRS associated with hae-mophagocytosis markers (spleen and liver enlargement, hyperferritinaemia > 10,000 ng/mL, hypofibrinogenemia.. .) should direct the diagnosis towards an overlapping CRS/MAS. An adap-ted treatment will be based on high-dose IV anakinra and corticosteroids and chemotherapy with etoposide at late refractory stages. These complications and others delignate the need of close collaboration with an intensive care unit.