BITE Therapy - Adverse Side Effects Information

MEDICAL GUIDANCE ONLY: This document provides general clinical guidance for emergency management of BiTE therapy complications. It does not replace clinical judgment, established protocols, or the medical decision-making of the treating healthcare provider. Treatment decisions should be tailored to individual patient needs and circumstances.

Dear Provider,

I am currently receiving treatment with a bispecific T-cell engager antibody, also known as BiTE therapy. BiTE therapy can cause potentially life-threatending adverse effects such as:

• Cytokine release syndrome (CRS)

• Immune effector cell-associated neurotoxicity syndrome (ICANS)

IF I HAVE A FEVER, PLEASE INCLUDE STEROIDS (DEXAMETHASONE) AS PART OF MY CARE PLAN.

While steroids (dexamethasone) are strongly recommended for fever in BiTE therapy patients as noted above, final treatment decisions should integrate the complete clinical assessment, patient history, and provider judgment.

POTENTIAL SIGNS AND SYMPTOMS

ICANS

Fever (100.4°F/38°C or higher)

Hypotension

Tachycardia

Difficulty breathing

Chills ± rigors

Dizziness/lightheadedness

Severe nausea, vomiting, and/or diarrhea

Severe muscle or joint pain

Headache

Treatment of Grade 1 CRS

(fever without hypotension or hypoxia)

• Acetaminophen

• Dexamethasone 4-12 mg PO or IV (optional)

• IV fluids (optional)

Treatment of Grade 2 CRS

(fever WITH hypotension ± hypoxia)

• All of the above PLUS:

• Admit to hospital

• Add low flow oxygen if hypoxic

• Tocilizumab 8 mg/kg (max 800 mg) IV x 1 over 1 hour

Treatment of Grade 3+ CRS

(fever WITH hypotension requiring vasopressor ± hypoxia requiring high flow oxygen or positive pressure)

• All of the above PLUS:

• Transfer to ICU

• Vasopressors as needed

• High flow oxygen or positive pressure ventilation as needed

Confusion

Altered consciousness

Agitation

Difficulty speaking Seizures

Loss of balance

Muscle weakness

Treatment of Grade 1 ICANS

• Start levetiracetam 500 mg by mouth twice daily

• Add dexamethasone 10 mg IV x 1 if also exhibiting CRS

Treatment of Grade 2 ICANS

• All of the above

• Repeat dexamethasone 10 mg IV after 6-12 hours if no improvement with first dose. Continue every 6-12 hours until grade 1 and then taper

• Add tocilizumab 8 mg/kg (max 800 mg) IV over 1 hour if also exhibiting CRS

Treatment of Grade 3+ ICANS

• All of the above

• Transfer to ICU

• If no improvement from dexamethasone, switch to methylprednisolone 1000 mg IV 1-2 times/day x 3 days followed by rapid taper

Grade

Fever

Hypotension

ASTCT GRADING OF CRS

Grade 3

Hypoxia

Grade 4

Temperature ≥38°C Temperature ≥38°C Temperature ≥38°C Temperature ≥38°C

None Not requiring vasopressors Requiring vasopressor ± vasopressin

None Requiring low-flow O2

• CRS grade is determined by the more severe event

Requiring multiple vasopressors (excluding vasopressin)

Requiring low-flow O2 Requiring positive pressure

• Fever is defined as temperature ≥ 38°C not attributable to any other causes. In patients who have CRS and receive antipyretic or anticytokine therapy (e.g., tocilizumab or steroids), fever is no longer required to grade subsequent CRS severity and should be driven by hypotension and/or hypoxia

• Low-flow O2: ≤ 6 L/min; low-flow nasal canula, blow-by

• High-flow O2: >6 L/min; high-flow nasal canula, nonrebreather mask, or Venturi mask

• Positive pressure: CPAP, BiPAP, intubation and mechanical ventilation

ASTCT = American Society for Transplantation and Cellular Therapy

ASTCT GRADING OF ICANS

ICE Score*

Depressed level of consciousness

Seizure

Motor findings

Elevated intracranial pressure/ cerebral edema

Grade 1

Grade 2

Grade 3

Awakens spontaneously Awakens to voice Awakens only to tactile stimulus

N/A

N/A

Any clinical seizure focal or generalized that resolved rapidly or nonconclusive serizures on EEG that resolve with intervention

Grade 4

Patient is unarousable; stupor or coma N/A

Focal/local edema on neuroimaging

Life-threatening prolonged seizure (>5 min.); or repetitive clinical or electrical seizures without return to baseline between

Deep focal motor weakness such as hemiparesis or paraparesis

Diffuse cerebral edema on neuroimaging; decerebrate or decorticate posturing; cranial nerve VI palsy; papilledema; or Cushing’s triad

*ICE Encephalopathy Assessment (0-10 point scale)

4 POINTS Orientation: orientation to year, month, city, hospital

3 POINTS Naming: ability to name 3 objects (e.g., point to clock, pen, button)

1 POINT Following commands: ability to follow simple commands (e.g., “Show me 2 fingers” or “Close your eyes and stick out your tongue”)

1 POINT Writing: ability to write a standard sentence (e.g., “Our national bird is the bald eagle.”)

1 POINT Attention: ability to count backwards from 100 by 10

This information is current as of March 2025. Treatment recommendations may evolve as clinical practice advances. Providers should verify against the most current guidelines available.