Differential diagnosis and workup of hypotension and hypoxemia in patients treated with CAR T-cell therapy
| Sign of CRS . | Differential diagnosis . | Workup . | Considerations . |
|---|---|---|---|
| Hypotension | Neutropenic sepsis and septic shock Cardiogenic shock (cardiac tamponade and acute coronary syndrome)∗ Hemorrhagic | •Obtain cultures, urinalysis, and chest radiograph•ECG, echocardiogram, and cardiac enzyme/natriuretic peptide level•Initiate empiric broad spectrum antibiotics•Resuscitation with IV fluids (3 mL/kg) and vasopressor support, if needed | •Workup should not delay treatment of CRS•Telemetry/ICU admission is recommended•Timing of symptom onset from CAR product infusion can help guide treatment and workup•During resuscitation, evaluation of patients’ intravascular status (bedside ultrasound vs noninvasive hemodynamic monitoring) is of importance because of the risk of capillary leakage when associated with CRS•Limited role of cardiac catheterization because of thrombocytopenia and inability to use anticoagulation or antiplatelet therapy |
| Hypoxemia | Infectious Pleural effusion† Cardiogenic and noncardiogenic pulmonary edema Thrombotic events | •Chest radiograph/CT chest•Sputum cultures, viral swabs, and fungal and viral titers for those at risk•Thoracentesis•Echocardiogram, ECG, and troponin and natriuretic peptide levels if clinical and imaging findings are suggestive of pulmonary edema•Lower extremity ultrasound/CTPA | •Cytology and flow cytometry for CAR T cells in pleural fluid (if available) can help differentiate the cause of effusion•Bronchoscopy can be considered in patients with persistent pulmonary infiltrates despite improvement of CRS symptoms (or low suspicion of CRS to be the cause of hypoxemia)•Workup should not delay the treatment of CRS•Timing of symptom onset from CAR T-cell infusion can help guide treatment and workup |
| Sign of CRS . | Differential diagnosis . | Workup . | Considerations . |
|---|---|---|---|
| Hypotension | Neutropenic sepsis and septic shock Cardiogenic shock (cardiac tamponade and acute coronary syndrome)∗ Hemorrhagic | •Obtain cultures, urinalysis, and chest radiograph•ECG, echocardiogram, and cardiac enzyme/natriuretic peptide level•Initiate empiric broad spectrum antibiotics•Resuscitation with IV fluids (3 mL/kg) and vasopressor support, if needed | •Workup should not delay treatment of CRS•Telemetry/ICU admission is recommended•Timing of symptom onset from CAR product infusion can help guide treatment and workup•During resuscitation, evaluation of patients’ intravascular status (bedside ultrasound vs noninvasive hemodynamic monitoring) is of importance because of the risk of capillary leakage when associated with CRS•Limited role of cardiac catheterization because of thrombocytopenia and inability to use anticoagulation or antiplatelet therapy |
| Hypoxemia | Infectious Pleural effusion† Cardiogenic and noncardiogenic pulmonary edema Thrombotic events | •Chest radiograph/CT chest•Sputum cultures, viral swabs, and fungal and viral titers for those at risk•Thoracentesis•Echocardiogram, ECG, and troponin and natriuretic peptide levels if clinical and imaging findings are suggestive of pulmonary edema•Lower extremity ultrasound/CTPA | •Cytology and flow cytometry for CAR T cells in pleural fluid (if available) can help differentiate the cause of effusion•Bronchoscopy can be considered in patients with persistent pulmonary infiltrates despite improvement of CRS symptoms (or low suspicion of CRS to be the cause of hypoxemia)•Workup should not delay the treatment of CRS•Timing of symptom onset from CAR T-cell infusion can help guide treatment and workup |
CT, computed tomography; CTPA, computed tomography pulmonary angiography; ECG, electrocardiogram.
Can also consider on-target off-tumor toxicities, decompensated pulmonary hypertension with right ventricular failure, and severe cardiomyopathy in the setting of CRS.
Can be present in CRS due to capillary leakage; however, heart failure, progression of malignant effusions, and empyema (in some cases) can also be causative.