CRS and ICANS After CAR-T or Bispecific Antibodies: Management

CRS and ICANS After CAR-T or Bispecific Antibodies: overview

This algorithm summarizes grade-based management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR-T cells or T-cell engaging bispecific antibodies, using ASTCT consensus grading. Infection must always be ruled out.

Grade 1 CRS (fever alone) is treated with antipyretics, fluids and an infection workup, with tocilizumab considered if it is prolonged after CAR-T. Grade 2 CRS (hypotension responsive to fluids or low-flow oxygen) is treated with tocilizumab 8 mg/kg intravenously (maximum 800 mg), repeatable every 8 hours up to three doses in 24 hours, adding dexamethasone 10 mg every 6 hours if it does not improve. Grade 3 to 4 CRS needs intensive care with tocilizumab and high-dose corticosteroids, using methylprednisolone 1 g daily for grade 4. Grade 1 ICANS is managed with supportive care, aspiration precautions and frequent ICE score checks. Grade 2 or higher ICANS is treated with dexamethasone 10 mg every 6 hours, escalating for grade 3 to 4; tocilizumab does not cross the blood-brain barrier and is not used for isolated ICANS. Steroid-refractory CRS or ICANS is treated with anakinra or siltuximab, and an HLH-like syndrome (IEC-HS) should be considered. No specific trials are linked to this chart.

Background reading: CAR-T and Engager Toxicity board review notes.

CRS and ICANS After CAR-T or Bispecific Antibodies: the algorithm in words

ASTCT grade-based management of cytokine release syndrome and neurotoxicity. Starting point: Fever, hypotension, hypoxia or neuro changes after CAR-T or bispecific. Full background: CAR-T and Engager Toxicity notes.

CRS grade 1 (fever) (first-line): Supportive: Antipyretics, fluids, rule out infection (consider tocilizumab if prolonged (CAR-T)).
CRS grade 2 (first-line): First: Tocilizumab 8 mg/kg IV (max 800 mg) (repeat every 8 h, max 3 doses in 24 h); Not improving: Add dexamethasone 10 mg every 6 h (fluids, low-dose pressor).
CRS grade 3-4 (first-line): ICU: Tocilizumab + high-dose steroids (methylprednisolone 1 g/day for grade 4).
ICANS grade 1 (first-line): Monitor: Supportive care, ICE score checks (aspiration precautions; neurology).
ICANS grade 2+ (first-line): Steroids: Dexamethasone 10 mg IV every 6 h (escalate for grade 3-4; no tocilizumab alone).
Steroid-refractory (first-line): Next: Anakinra or siltuximab (consider HLH-like syndrome (IEC-HS)).

Simplified board-prep scaffold; verify against current guidelines (ASTCT grading, product labels). Always rule out infection. Tocilizumab does not cross the blood-brain barrier and does not treat isolated ICANS. Seizure prophylaxis with levetiracetam is common with CAR-T. Bispecifics use step-up dosing; CRS is mostly grade 1 to 2 and occurs with the first doses.