CRS/ICANS Quick Reference

All Grades

ALL

All CRS Grades — IEC

Universal interventions

⌄

Rule out infection, disease progression

Acetaminophen 650 mg PO Q6H PRN temp ≥ 38°C (may substitute ibuprofen 200mg Q4H if needed)

Empiric broad-spectrum abx if neutropenic

Symptomatic/supportive care as indicated

Graded Management

1

Grade 1 CRS

Temp ≥ 38°C only

⌄

Acetaminophen 650 mg PO Q6H PRN

Consider Dexamethasone 10 mg IV Q24H for early-onset CRS (<72h after infusion)

Consider Tocilizumab 8 mg/kg IV over 1h (max 800 mg) if persistent fever >48h. AVOID if concurrent ICANS

Sepsis screen + empiric broad-spectrum abx

Maintenance IV fluids

2

Grade 2 CRS

Temp + hypotension (no pressors) and/or O₂ ≤ 6L

⌄

Dexamethasone 10 mg IV × 1. May repeat Q12H

If no improvement after dex within 12h: Tocilizumab 8 mg/kg IV (max 800 mg). Repeat Q8H (max 3 doses/24h; 4 doses total)

IV fluid bolus PRN

Low-flow O₂ nasal cannula + cardiac monitoring

Escalate to Grade 3 management if no improvement within 24h of tocilizumab

3

Grade 3 CRS

Vasopressor required and/or O₂ >6L

⌄

ICU care + echocardiogram

Dexamethasone 10 mg IV × 1. Repeat Q6H until improvement. If refractory → Grade 4

Tocilizumab 8 mg/kg IV (max 800 mg). Repeat Q8H until improvement (max 3/24h, 4 total)

IV fluid bolus + vasopressors PRN

Cardiac/hemodynamic monitoring + supplemental O₂

4

Grade 4 CRS

Multiple pressors and/or positive pressure O₂

⌄

ICU care, cardiac/hemodynamic monitoring + ECHO

Dexamethasone 10 mg IV × 1 STAT, then Methylprednisolone 1000 mg IV Q24H × 3 days. If refractory: Q12H

Tocilizumab 8 mg/kg IV (max 800 mg). Repeat Q8H (max 3/24h, 4 total)

Multiple vasopressors (excl. vasopressin) + positive pressure (CPAP/BiPAP/intubation)

If refractory: add Anakinra or Siltuximab

★ Consult pharmacy for rapid steroid taper when discontinuing

After antipyretics/anticytokines administered, CRS grading is driven by hypotension/hypoxia only — fever no longer required.

All Grades

ALL

All CRS Grades — BsAb

Universal interventions

⌄

Hold bispecific antibody if indicated (see Rechallenge tab)

Acetaminophen 650 mg PO Q6H PRN temp ≥ 38°C

Empiric broad-spectrum abx if neutropenic

Symptomatic/supportive care

BLINCYTO: continue if Grade 1-2. KIMMTRAK: continue if Grade 1.

Graded Management

1

Grade 1 CRS

Temp ≥ 38°C only

⌄

Acetaminophen 650 mg PO Q6H PRN

Consider Dexamethasone 10 mg PO/IV × 1 dose

Consider maintenance IV fluids

If persistent/refractory fever >48h → manage as Grade 2

2

Grade 2 CRS

Temp + hypotension (no pressors) and/or O₂ ≤ 6L

⌄

Assess need for inpatient care

Dexamethasone 10 mg PO/IV × 1. May repeat Q12H

IV bolus PRN + low-flow O₂ + cardiac monitoring

If symptoms persist >24h: Tocilizumab 8 mg/kg IV (max 800 mg). Repeat Q8H if no improvement (max 3/24h, 4 total)

3

Grade 3 CRS

Vasopressor required and/or O₂ >6L

⌄

ICU care

Dexamethasone 10 mg IV × 1. Repeat Q6H until improvement

Tocilizumab 8 mg/kg IV (max 800 mg). Repeat Q8H (max 3/24h, 4 total)

IV fluids + vasopressors + cardiac/hemodynamic monitoring

If refractory → Grade 4 management

4

Grade 4 CRS

Multiple pressors and/or positive pressure O₂

⌄

ICU care

Permanently discontinue bispecific antibody

Methylprednisolone 1000 mg IV Q24H × 3 days

Tocilizumab 8 mg/kg IV (max 800 mg). Repeat Q8H (max 3/24h, 4 total)

Multiple vasopressors (excl. vasopressin) + positive pressure + ECHO

If refractory: add Anakinra or Siltuximab

★ Consult pharmacy for rapid steroid taper when discontinuing

⚡

Seizure Prophylaxis Start on day of infusion if elevated ferritin (>400) or CRP >4. Levetiracetam 500–750 mg Q12H × 30 days. Renally adjust per practice.

All Grades

ALL

All ICANS Grades — IEC

Universal measures

⌄

Assess swallow, withhold oral intake if indicated, aspiration precautions

Avoid CNS-sedating medications

Neurology consult if Grade 2 or higher

Neuroimaging Q2–3 days if persistent ICANS

Consider LP if Grade 1 persists >48h or Grade 2+ >24h

Graded Management

1

Grade 1 ICANS

ICE 7–9 · Awakens spontaneously

⌄

Dexamethasone 10 mg IV × 1 and reassess

Consider Levetiracetam 750 mg PO/IV Q12H based on risk

2

Grade 2 ICANS

ICE 3–6 · Awakens to voice

⌄

Dexamethasone 10 mg IV × 1. If unresolved/progressing → Q6–12H

Consider Levetiracetam 750 mg IV Q12H based on risk

3

Grade 3 ICANS

ICE 0–2 · Tactile stimulus · Seizure · Local edema

⌄

ICU care

Dexamethasone 10 mg IV Q6H. If no improvement to Grade 2 after 24h → Methylprednisolone 1000 mg IV daily × 3 days

If steroid-refractory: Anakinra 100 mg Q6H

Levetiracetam 750 mg IV Q12H

Consider repeat neuroimaging

★ Consult pharmacy for rapid steroid taper when discontinuing

4

Grade 4 ICANS

ICE 0 · Unarousable · Prolonged seizure · Diffuse edema

⌄

ICU care, consider mechanical vent for airway protection

Methylprednisolone 1000 mg IV Q12H

If steroid-refractory: Anakinra 100 mg Q6H

Levetiracetam 750 mg IV Q12H

Consider repeat neuroimaging

Consider antifungal prophylaxis with high-dose steroids

★ Consult pharmacy for rapid steroid taper when discontinuing

⚠ Concurrent CRS + ICANS (if CRS Grade 2+)

ICANS GradeAdditional Therapy

Add tocilizumab for all grades if concurrent CRS ≥2

G1

Tocilizumab 8mg/kg IV (max 800mg). Repeat Q8H PRN (max 3/24h, 4 total)

G2

Same as G1 + consider ICU if neuro assoc. w/ CRS ≥2

G3

Same as G1 + ICU care

G4

Same as G1 + ICU care

Grade 1 ICANS + Grade 1 CRS: manage per standard chart above — no extra toci needed.

All Grades

ALL

All ICANS Grades — BsAb

Universal measures

⌄

Hold bispecific antibody if indicated (see Rechallenge)

Assess swallow, withhold oral intake if indicated, aspiration precautions

Avoid CNS-sedating medications

Neurology consult if Grade 2 or higher

Neuroimaging Q2–3 days if persistent

Consider LP if Grade 1 >48h or Grade 2+ >24h

BLINCYTO: continue if Grade 1–2. KIMMTRAK: continue if Grade 1.

Graded Management

1

Grade 1 ICANS

ICE 7–9 · Awakens spontaneously

⌄

Dexamethasone 10 mg IV × 1. If unresolved/progressing → Q6H

Consider Levetiracetam 750 mg PO/IV Q12H based on risk

2

Grade 2 ICANS

ICE 3–6 · Awakens to voice

⌄

Dexamethasone 10 mg IV Q6H

Consider Levetiracetam 750 mg IV Q12H based on risk

3

Grade 3 ICANS

ICE 0–2 · Tactile stimulus · Seizure · Local edema

⌄

ICU care

Dexamethasone 10 mg IV Q6H. If no improvement to Grade 2 after 24h → Methylprednisolone 1000 mg daily × 3 days

If steroid-refractory: Anakinra 100 mg Q6H

Levetiracetam 750 mg IV Q12H + consider repeat neuroimaging

★ Consult pharmacy for rapid steroid taper

4

Grade 4 ICANS

ICE 0 · Unarousable · Prolonged seizure

⌄

ICU care, consider mechanical vent for airway protection

Methylprednisolone 1000 mg IV Q12H

If steroid-refractory: Anakinra 100 mg Q6H

Levetiracetam 750 mg IV Q12H + repeat neuroimaging

Consider antifungal prophylaxis with high-dose steroids

★ Consult pharmacy for rapid steroid taper

📊 ICE Score Calculator

ICANS grade = most severe domain. ICE score: orientation(4) + naming(3) + commands(1) + writing(1) + attention(1)

1. Orientation (year, month, city, hospital) — max 4 pts

2. Naming (3 objects) — max 3 pts

3. Follow commands (1 command) — max 1 pt

4. Write a standard sentence — max 1 pt

5. Attention (count backwards 100 by 10) — max 1 pt

10

Normal (Grade 0)

Awakens spontaneously

ICANS Grade Criteria

Domain	G1	G2	G3	G4
ICE	7–9	3–6	0–2	0 (unarousable)
Consciousness	Spontaneous	To voice	To tactile	Stupor/coma
Seizure	—	—	Resolves rapidly	>5 min or repetitive
Motor	—	—	—	Hemi/paraparesis
ICP/Edema	—	—	Focal edema	Diffuse, Cushing's

CRS — IEC Therapies

Agent	CRS Onset	Duration	Risk
AxicabtageneYESCARTA	2–4d	6–7d	90–93%
BrexucabtageneTECARTUS	5d*	7–8d*	91–92%
CiltacabtageneCARVYKTI	8d	3d	84%
IdecabtageneABECMA	1d	7d	84–88%
LisocabtageneBREYANZI	4–5d	4–5d	49–54%
ObecabtageneAUCATZYL	7–10d	5d	69–75%
TisagenlecleucelKYMRIAH	3–4d*	7–8d*	70–80%
AfamitresgeneTECELRA	2d	3d	75%

ICANS — IEC Therapies

Agent	ICANS Onset	Duration	Risk
AxicabtageneYESCARTA	4–5d	5–10d	45–54%
BrexucabtageneTECARTUS	6d*	21d*	30–60%
CiltacabtageneCARVYKTI	8d	6d	13–23%
IdecabtageneABECMA	2d	8d	18–21%
LisocabtageneBREYANZI	5–8d	5–7d	27–31%
ObecabtageneAUCATZYL	8–12d	8d	22–24%
TisagenlecleucelKYMRIAH	6d*	6–14d*	17–22%
AfamitresgeneTECELRA	2d	1d	~2%

Agent	CRS Onset	Duration	Risk
TebentafuspKIMMTRAK	Day of infusion	2d	88%
TalquetamabTALVEY	27h	17h	77–80%
TeclistamabTECVAYLI	2d	2d	72%
GlofitamabCOLUMVI	14h	2d	63–70%
TarlatamabIMDELLTRA	13.5h	4d	52–60%
EpcoritamabEPKINLY	24h	2d	50–51%
LinvoseltamabLYNOZYFIC	11h	15h	46%
ElranatamabELREXFIO	2d	2d	58%
BlinatumomabBLINCYTO	2d	5d	11–15%

Agent	ICANS Onset	Duration	Risk
TarlatamabIMDELLTRA	~16d	~4d	10%
TalquetamabTALVEY	~3d	~2d	9%
BlinatumomabBLINCYTO	≤14d	14d	8%
LinvoseltamabLYNOZYFIC	~1d	~2d	8%
TeclistamabTECVAYLI	~4d	~3d	6%
EpcoritamabEPKINLY	~3d	~2d	6%
GlofitamabCOLUMVI	N/A	~2d	5%
ElranatamabELREXFIO	~3d	~2d	3%
TebentafuspKIMMTRAK	N/A	N/A	1%

*Varies by indication

🚫

CAR-T is a one-time infusion There is no rechallenge protocol for IEC/CAR-T therapies. CRS/ICANS management focuses on treating the current episode.

CRS Rechallenge

Glofitamab IV / Mosunetuzumab IV

Current DoseG1G2: Interrupt; resume at 50% rate if resolved

G3: Hold

Next DoseG1G2: CRS resolved ≥72h before next

G3: Hospitalize for 24h

Elranatamab · Linvoseltamab · Talquetamab · Teclistamab SQ

Current DoseHold if not already completed

Next DoseG1G2: CRS resolved ≥24h
G3: Hospitalize ≥48h

Epcoritamab SQ

Current DoseHold if not already completed

Next DoseG1G2: CRS resolved ≥24h
G3: Hospitalize ≥24h

Blinatumomab (continuous IV)

Current DoseG1G2: Continue
G3: Interrupt; resume 9 mcg/d → escalate to 28 mcg/d after 7d

Next DoseN/A (continuous)

Tarlatamab IV

Current DoseHold; resume at next scheduled dose if resolved

Next DoseG1: Resolved ≥24h
G2G3: Resolved + hospitalize ≥22h

Tebentafusp IV

Current DoseG1: Continue
G2: Hold if not given
G3 (1st): Hold
G3 (recurrent/>48h): Discontinue

Next DoseG2 recurrent: Premedicate dex 4mg PO 30min prior
G3 recurrent: Permanently discontinue

All Grade 4 → Permanently Discontinue

ICANS Rechallenge

Mosunetuzumab IV

Current DoseG1: Continue
G2G3: Hold

Next DoseG2/G3: Resume if resolved to G1/baseline ≥72h; G3 recurrent: Permanently discontinue

Glofitamab IV

Current DoseG1: Continue
G2: Hold until G1/baseline
G3: Hold

Next DoseG3: Resume if resolved to G1/baseline ≥7 days

Elranatamab · Linvoseltamab · Talquetamab · Teclistamab SQ

Current DoseHold

Next DoseG2/G3: Resume if resolved to G1/baseline; G3 recurrent: Permanently discontinue

Blinatumomab (continuous IV)

Current DoseG1G2: Continue
G3: Hold until G1 ≥3d; resume 9 mcg/d → 28 mcg/d after 7d

Next DoseG3 at 9 mcg/d or no improvement to G1 within 7d: Permanently discontinue

Tarlatamab IV

Current DoseHold; resume at next scheduled dose if resolved

Next DoseG3: No improvement to G1 within 7d or recurrent G3 → permanently discontinue

Tebentafusp IV

Current DoseHold

Next DoseHold until G1/baseline; same dose, no escalation if G3 during initial dose; resume escalation once tolerated

CRS / ICANS Guide

⚠ Concurrent CRS + ICANS (if CRS Grade 2+)

📊 ICE Score Calculator

Glofitamab IV / Mosunetuzumab IV

Elranatamab · Linvoseltamab · Talquetamab · Teclistamab SQ

Epcoritamab SQ

Blinatumomab (continuous IV)

Tarlatamab IV

Tebentafusp IV

All Grade 4 → Permanently Discontinue

Mosunetuzumab IV

Glofitamab IV

Elranatamab · Linvoseltamab · Talquetamab · Teclistamab SQ

Blinatumomab (continuous IV)

Tarlatamab IV

Tebentafusp IV

All Grade 4 → Permanently Discontinue