Table 4 Monitoring and management of toxicities associated with CAR-T therapy
From: Immunotherapy in hematologic malignancies: achievements, challenges and future prospects
CAR-T therapy-related AEs | Biomarkers to monitor | Toxicity management |
|---|---|---|
CRS | CRP, IFN-γ, IL-1, IL-2, IL2Rα, IL-4, IL-6, IL-8, IL-10, TNF-α, granzyme B, MIP-1α, MCP-1, and GM-CSF in PB | Grade 1: broad-spectrum antibiotics along with supportive care; Grade ≥2: Intravenous tocilizumab ≤4 doses; Grade ≥3 and in cases of grade 2 toxicity with sustained hypotension after anti-IL-6 therapy: add corticosteroids; Refractory to both tocilizumab and corticosteroids: use other agents include the Janus-associated kinase inhibitor, cyclophosphamide, extracorporeal cytokine adsorption with continuous renal replacement therapy, IVIG and anti-thymocyte globulin. |
Neurotoxicity | IL-1, IL-6, IFN-γ, TNF-α/β, CRP, coagulation markers, ferritin in PB; MCP1, IL-6, IL-8 in CSF; ICE score | Grade ≥1 ICANS: monitoring, supportive care and corticosteroids alone; Tocilizumab was not recommended unless patients have concurrent CRS. |
HLH/MAS | Blood routine test; IFN-γ, IL-6, GM-CSF, CRP, ferritin in PB | Suppress the overactive immune cells; Corticosteroids, anakinra or intrathecal cytarabine can be considered in cases when the HLH/MAS is caused by resistance to tocilizumab. |
CARAC | Primary coagulation markers including platelet count in PB, APTT, PT, FIB, FDP, and D-dimer; test for CRS | Management of CRS; replacement therapy to decrease the risk of bleeding and control active bleeding, including the transfusion of platelet, fresh frozen plasma and prothrombin complex concentrates and fibrinogen and cryoprecipitate; anticoagulant therapy and/or antifibrinolytic therapy should be used as appropriate for patients with high-grade CRS. |
Cytopenia | Blood routine test, CRP, ferritin in PB; cytology of blood marrow | Growth factors, thrombopoietin receptor agonists, stem cell enhancement, transfusion support; Elimination of infectious risk |
Hypogammaglobulinemia | Gammaglobulinemia in PB | Intravenous or subcutaneous immunoglobulin G |
Infection | IL-6, CRP in PB; lymphocyte count; CT of lungs; viral and bacterial etiologic test | Provide antibacterial or antifungal prophylaxis; For certain patients with concurrent severe or recurrent infections and hypogammaglobulinemia: IVIG is recommended as replacement treatment. |
ADAs | Detection of ADAs in serum (HAMA is the ADA occurred in CAR-T therapy with murine-derived scFv) | Secondary reinfusion by altering the target and strengthening lymphodepletion. |
