TABLE 2.
Adverse reactions related to CAR-T cell therapy.
| Adverse reaction | Main symptoms | Relationship with CRS | Characteristic |
|---|---|---|---|
| CRS | Fever; Hypotension; Hypoxia; DIC; Multi organ system toxicities | — | • Systemic inflammatory reaction caused by a large number of inflammatory factors |
| ICANS | Aphasia; Headache; Mild encephalopathy; Focal neurological Deficit; Tremor; Seizures; brain edema | CRS is one of the main inducers of ICANS, ICANS and CRS may occur simultaneously or not | • The breakdown of the BBB and capillary leakage lead to the entry of pro-inflammatory cytokines and CAR-T cells into the CSF to damage the CNS. |
| Cardiovascular toxicity | Hypotension; Sinus tachycardia; Increased serum troponin levels; Arrhythmia; Reduced LVEF; Cardiogenic shock; QT prolongation; Heart failure | CRS is one of the main inducers of cardiovascular toxicity, which can lead to serious direct and indirect cardiovascular complications | • Abnormal elevation of inflammatory cytokines IL-6, VWF, Ang-2, TNF-α and off-target cross-reaction of CAR-T cells to actin can lead to cardiovascular toxicity |
| Hematologic toxicity | Neutropenia; Thrombocytopenia; Leucopenia; Anemia; B-cell aplasia; Coagulopathy | Patients with severe CRS were more likely to develop late hematologic toxicity | • Neutropenia is closely related to infectious complications |
| • B-cell aplasia is a common toxicity of anti-CD19 CAR-T therapy | |||
| HLH/MAS | Ferritin is extremely elevated; High fever; Hepatosplenomegaly; Hemocytopenia; Coagulopathy | HLH/MAS is a severe manifestation of CRS, so it is difficult to distinguish diagnosis of them | • The incidence of HLH/MAS is low, but its mortality is high and prognosis is poor |
| Skin toxicity | Rash; Dry skin; Purpura; Papules; Maculopapular; Urticarial rash; Bullous eruptions; Oral mucositis | CRS is one of the inducers of skin toxicity, and the reduced immune function induced by CRS may lead to skin infections in patients | • The clinical manifestations and mechanisms of skin toxicities are still poorly understood |
| • Currently, there are no guidelines to diagnose and treat skin toxicity | |||
| Pulmonary toxicity | Respiratory failure | CRS is one of the main inducers of pulmonary toxicity | • The incidence of pulmonary toxicity is lower than that of CRS and ICANS. |
| • There are definite clinical diagnostic indicators about pulmonary toxicity | |||
| Renal toxicity | Adrenal insufficiency; Electrolyte disorders; Kidney failure; Acidosis | CRS is one of the main inducers of renal toxicity | • The incidence of renal toxicity is lower than that of CRS and ICANS. |
| • There are definite clinical diagnostic indicators about renal toxicity | |||
| • Usually symptomatic treatment | |||
| Hepatotoxicity | Liver injury | CRS is one of the main inducers of hepatotoxicity | • The incidence of hepatotoxicity is lower than that of CRS and ICANS. |
| • There are definite clinical diagnostic indicators about hepatotoxicity | |||
| Gastrointestinal toxicity | Diarrhea; Vomiting; Bleeding; Nausea | CRS is one of the main inducers of gastrointestinal toxicity | • The incidence of gastrointestinal toxicity is lower than that of CRS and ICANS. |
| • There are definite clinical diagnostic indicators about gastrointestinal toxicity | |||
| • Usually symptomatic treatment |
CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; DIC, disseminated intravascular coagulation; BBB, blood brain barrier; CSF, cerebrospinal fluid; CNS, central nervous system; LVEF, left ventricular ejection fraction; IL, interleukin; Ang-2, angiopoietin-2; VWF, von willebrand factor; TNF-α, tumor necrosis factor alpha; HLH/MAS, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome.