The 2019 ASTCT consensus definitions for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome became the common language for cell therapy toxicity — adopted by clinicians, investigators and sponsors, and the basis for the treatment algorithms in use. Since then the recognised toxicity spectrum has widened, and this update addresses what the original criteria did not cover.
Two tasks were set. The first was to revise the existing grading for cytokine release syndrome, ICANS and immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome. The second was to define toxicities that had no agreed criteria at all: immune effector cell-associated haematotoxicity, enterocolitis, tumour inflammation-associated neurotoxicity, on-target off-tumour toxicity, and — the part that lands on neurology — non-ICANS neurological toxicities including parkinsonism, cranial nerve palsies and polyneuropathies.
That last group is the reason a neurologist should read this. Delayed movement disorders and cranial neuropathies after CAR T-cell therapy have until now been graded, if at all, against criteria written for an encephalopathy they do not resemble, which meant they were recorded inconsistently and managed by improvisation. A named, graded syndrome is what connects the presentation to a management pathway and makes the incidence countable. If you take neurology referrals from a cell therapy service, agree now which grading version the joint notes will use.
- Agree with your cellular therapy service which version of the ASTCT criteria the notes use
- Grade delayed parkinsonism and cranial neuropathies as non-ICANS toxicity rather than forcing them into ICANS
- Apply the criteria to T-cell engager therapy as well — the update covers both
- Record the grading scale version in the note, because trial and real-world comparisons depend on it
- Note that grading criteria define severity; the management algorithms sit in separate guidance
Why it matters
Delayed neurological toxicity after cell therapy has had no agreed grading, so it has been recorded inconsistently and managed case by case.
Don't overread it
This is consensus grading, not a management guideline — it defines severity without telling you what to give.
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