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ICANS grade (ASTCT Criteria) calculator

Complete all items below to get ICANS grade.

ICE Score The Immune effector Cell Encephalopathy (ICE) score forms one component of the ASTCT ICANS grading system.

ICE is a 10 point scoring system of signs and symptoms associated with immune therapy related encephalopathy.

Is the patient oriented to:

Year:

Month:

City:

Hospital:


Is the patient able to:
Name three objects? e.g. point to a clock, pen, button
3 objects named correctly
2 objects named correctly
1 object named correctly
No object named correctly

Follow simple commands? e.g. show me 2 fingers or close your eyes and show me your tongue.

Write a sentence? e.g. Our national bird is the bald eagle.

Patients may have difficulty writing a sentence due to apraxia or poor handwriting.

Count backward from 100 in tens?

ICE SCORE:


Other ICANS paramaters
Level of consciousness A depressed level of consciousness should not be due to any other cause e.g. sedative medication
Awakens spontaneously
Awakens to voice
Awakens only to tactile stimulus
Unarousable
OR
requires vigorous/ repetitive tactile stiumli to arouse
OR
stupor / coma.


Seizures
No seizure events
Any clinical seizure, focal or generalised, that resolves rapidly
OR
Non-convulsive seizure on EEG that resolves with intervention.
Life threatening prolonged seizure (>5 mins)
OR
Repetitive clinical or electrical seizures without return to baseline in between
Motor findings Tremors and myoclonus can be recorded according to CTCAE grading but do not impact ICANS grading.
No focal motor changes
Deep focal motor weakness e.g. hemiparesis or paraparesis
Elevated ICP/ cerebral edema Intracerebral haemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from ICANS grading.
No edema present on neuroimaging
Focal/ local edema on neuroimaging
Diffuse cerebral edema on neuroimaging
OR
Decerebrate/ decorticate posturing
OR
Cranial nerve VI palsy
OR
Papilledema
OR
Cushing's triad Bradycardia, irregular breathing, widened pulse pressure.
Score:

ASTCT ICANS (Immune effector Cell Associated Neurotoxicity Syndrome) Grade calculator

Immune effector Cell Associated Neurotoxicity Syndrome (ICANS) is a central nervous system disorder that may develop following any immune therapy that activates or engages endogenous or infused immune effector cells (e.g. CAR-T cell therapy).

This grading system is only suitable for patients ≥12 years and with baseline cognitive ability to perform the ICE assessment .

Clinical features of ICANS includes altered level of consciousness, aphasia, cognitive impairment, motor weakness and seizures. The symptoms are usually progressive with the earliest symptoms including inattention, language disturbance and impaired handwriting (1,2).

The ASTCT ICANS grading system is a consensus guideline based on expert opinion(3). It consists of a 10-point encephalopathy screening tool called ICE followed by evaluation of other domains including consciousness, motor symptoms, signs of raised ICP/ cerebral edema. The overall ICANS grade is based on the most severe score out of all domains.

The other major toxicity associated with cellular immune therapies is cytokine release syndrome (CRS). CRS typically precedes ICANS, although concurrent occurrence is possible. Patients who develop ICANS commonly had preceding CRS. Both ICANS and CRS are usually reversible with appropriate management.

The table below summarises a proposed management guideline according to ICANS grade(2,4).

See also the ASTCT CRS grading system.

Please note that management and grading of ICANS is an emerging field with guidelines expected to change in the near future. Please ensure to check latest guidelines.
ICANS Grade Management
1
  • Supportive measures (aspiration prevention, assess swallow, IV fluids)
  • EEG, consider brain MRI and diagnostic lumbar pressure including opening pressure.
  • Fundoscopy and neurological consultation
  • If associated with CRS: Consider tocilizumab. Consider adding steroids if no improvement after the first dose of tocilizumab.
2
  • As per grade 1
  • If no CRS: Consider dexamethasone 10mg IV every 6 hours. Wean steroids once improved to G1.
  • If associated with CRS: Give tocilizumab. If no improvement after first dose of tocilizumab commence dexamethasone 10mg IV every 6 hours.
  • If associated with CRS grade ≥2: Consider management in ICU setting.
3
  • As per grade 1 and 2 above
  • Manage in ITU setting
  • If no CRS: Dexamethasone 10mg IV every 6 hours.
  • If associated with CRS: Give tocilizumab. If no improvement after first dose of tocilizumab commence dexamethasone 10mg IV every 6 hours.
4
  • As per grades 1 to 3 above
  • If no CRS Methylprednisilone 1g IV 1-2 times per day for 3 days.
  • If not improving, increase to methylprednisolone 1g IV 2-3 times per day for 3 days. Consider alternative therapies e.g. anakinra, cyclophosphamide, siltuximab,ruxolitinib, anti-thymocyte globulin.
  • Manage seizures as per local guidelines
  • If associated with CRS: Give tocilizumab as above. Also give methylprednisolone 1g IV 1-2 times per day for 3 days.

References:
  1. Morris EC, Neelapu SS, Giavridis T, Sadelain M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol. 2022;22(2):85-96. doi:10.1038/s41577-021-00547-6
  2. Neelapu SS. Managing the toxicities of CAR T-cell therapy. Hematol Oncol. 2019;37(S1):48-52. doi:https://doi.org/10.1002/hon.2595
  3. Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol blood marrow Transplant J Am Soc Blood Marrow Transplant. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758
  4. Santomasso BD, Nastoupil LJ, Adkins S, et al. Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. J Clin Oncol. 2021;39(35):3978-3992. doi:10.1200/JCO.21.01992