Prevention, monitoring, and management of CRS, ICANS, and delayed neurotoxicity
| . | Prevention . | Monitoring . | Management . |
|---|---|---|---|
| CRS | Potential risk factors: high disease burden, aggressive disease • When clinically feasible, consider bridging therapy to reduce disease burden or use CAR-T cell therapy therapy in lower disease burden state | • Temperature and vital signs • Laboratory tests: CBC, chemistry, CRP, ferritin, coagulation studies | Any grade: • Supportive care: antipyretics • IV fluid hydration • Supplemental oxygen • Assessment of infection and, if neutropenic, empiric antibiotics per neutropenic guidelines Grades 1 and 2: consider tocilizumab for grade 1 CRS based on clinical features, especially if persistent. Recommend tocilizumab + corticosteroids for grade ≥2 CRS, with dosing and frequency based on severity. Grade ≥3: • Vasopressor support • Tocilizumab + corticosteroids • Second line: anakinra, siltuximab, etanercept, infliximab, lenzilumab |
| ICANS | Potential risk factors: disease burden, baseline elevated inflammatory markers, higher CAR T-cell dose • When clinically feasible, consider bridging therapy to reduce disease burden or use CAR T-cell therapy in lower disease burden state • Antiseizure prophylaxis | • Neurologic consultation in patients with preexisting neurologic disease • Baseline neurologic and mental status exams • ICE score every 8 hours • Neurologic checks at least every 8 hours • Airway monitoring | Any grade: • Supportive care: aspiration precautions, seizure prophylaxis • Corticosteroids: dosing and frequency dependent on severity • Consider CT head, MRI brain, EEG, and neurologic consultation Grade ≥3: • High-dose corticosteroids • Second line: anakinra, siltuximab |
| Delayed neurotoxicity | Risk factors: high disease burden, CRS, ICANS • Timely treatment of CRS/ICANS • When clinically feasible, consider bridging therapy to reduce disease burden or use CAR T-cell therapy in lower disease burden state | • Neurologic consultation in patients with preexisting neurologic disease • Neurologic evaluation up to 1 year after infusion to evaluate for cranial nerve palsies, neuropathy, and Parkinsonism | • Supportive care • Neurologic consultation • Cranial nerve palsies: corticosteroids, consider IVIG • No known effective therapy for Parkinsonian features |
| IEC-HS | Unknown | • As in CRS with close monitoring of blood counts, liver and renal function, and coagulation parameters | • Supportive care: antipyretics, analgesics, IV fluid hydration, vasopressor support, correction of coagulopathy • Corticosteroids + anakinra • Second line: ruxolitinib, etoposide, emapalumab, activation of CAR T-cell “kill switches” • Evaluation and treatment of alternative etiologies, including infection and progressive disease |
| . | Prevention . | Monitoring . | Management . |
|---|---|---|---|
| CRS | Potential risk factors: high disease burden, aggressive disease • When clinically feasible, consider bridging therapy to reduce disease burden or use CAR-T cell therapy therapy in lower disease burden state | • Temperature and vital signs • Laboratory tests: CBC, chemistry, CRP, ferritin, coagulation studies | Any grade: • Supportive care: antipyretics • IV fluid hydration • Supplemental oxygen • Assessment of infection and, if neutropenic, empiric antibiotics per neutropenic guidelines Grades 1 and 2: consider tocilizumab for grade 1 CRS based on clinical features, especially if persistent. Recommend tocilizumab + corticosteroids for grade ≥2 CRS, with dosing and frequency based on severity. Grade ≥3: • Vasopressor support • Tocilizumab + corticosteroids • Second line: anakinra, siltuximab, etanercept, infliximab, lenzilumab |
| ICANS | Potential risk factors: disease burden, baseline elevated inflammatory markers, higher CAR T-cell dose • When clinically feasible, consider bridging therapy to reduce disease burden or use CAR T-cell therapy in lower disease burden state • Antiseizure prophylaxis | • Neurologic consultation in patients with preexisting neurologic disease • Baseline neurologic and mental status exams • ICE score every 8 hours • Neurologic checks at least every 8 hours • Airway monitoring | Any grade: • Supportive care: aspiration precautions, seizure prophylaxis • Corticosteroids: dosing and frequency dependent on severity • Consider CT head, MRI brain, EEG, and neurologic consultation Grade ≥3: • High-dose corticosteroids • Second line: anakinra, siltuximab |
| Delayed neurotoxicity | Risk factors: high disease burden, CRS, ICANS • Timely treatment of CRS/ICANS • When clinically feasible, consider bridging therapy to reduce disease burden or use CAR T-cell therapy in lower disease burden state | • Neurologic consultation in patients with preexisting neurologic disease • Neurologic evaluation up to 1 year after infusion to evaluate for cranial nerve palsies, neuropathy, and Parkinsonism | • Supportive care • Neurologic consultation • Cranial nerve palsies: corticosteroids, consider IVIG • No known effective therapy for Parkinsonian features |
| IEC-HS | Unknown | • As in CRS with close monitoring of blood counts, liver and renal function, and coagulation parameters | • Supportive care: antipyretics, analgesics, IV fluid hydration, vasopressor support, correction of coagulopathy • Corticosteroids + anakinra • Second line: ruxolitinib, etoposide, emapalumab, activation of CAR T-cell “kill switches” • Evaluation and treatment of alternative etiologies, including infection and progressive disease |
CBC, complete blood count; CRP, C-reactive protein; EEG, electroencephalogram; ICE, immune effector cell-associated encephalopathy.