ICANS MANAGEMENT
AT INDIAN CAR-T CENTRES
NexCAR19 carries one of the lowest ICANS profiles of any approved CAR-T product. Indian centres have structured neurology support and dexamethasone-based protocols for all grades.
analyticsAt a Glance
- check_circle15% any-grade ICANS incidence with NexCAR19 pivotal trial โ 0% grade 4
- check_circleLower neurotoxicity profile than axicabtagene ciloleucel (axi-cel)
- check_circleDexamethasone 10 mg IV q6h standard for grade 2+ at TMC, Apollo, AIIMS
- check_circleLevetiracetam antiseizure prophylaxis given to all CAR-T patients
What Is ICANS and Why Does It Occur?
ICANS is a neurological complication of CAR-T therapy caused by inflammatory cytokines crossing the blood-brain barrier. It ranges from mild confusion to rare severe cerebral oedema.
Mechanism
Activated CAR-T cells and macrophages release cytokines (IL-6, IFN-ฮณ, TNF-ฮฑ) that disrupt the blood-brain barrier. Endothelial activation allows inflammatory mediators into the CNS, causing dysfunction.
Timing
ICANS typically begins 4โ10 days post-infusion, often overlapping with or following the peak of CRS. Grade 1โ2 symptoms are most common; grade 3โ4 is rare with NexCAR19.
NexCAR19 Advantage
The pivotal trial of NexCAR19 (ImmunoACT) reported 15% any-grade ICANS and 0% grade 4 โ substantially lower than axi-cel (64% any-grade, 28% grade 3โ4) in comparable B-cell malignancy populations.
Why Lower with NexCAR19
NexCAR19 uses a humanised anti-CD19 scFv and a modified co-stimulatory domain thought to reduce excessive cytokine production. The exact mechanism of the reduced neurotoxicity profile is under investigation.
Symptoms to Watch: ICANS Warning Signs
Recognising early ICANS symptoms allows prompt intervention before progression to higher grades. Patients and caregivers should be briefed on these signs before discharge from the CAR-T unit.
Confusion and Disorientation
Inability to follow simple commands, disorientation to time or place, difficulty naming objects. Often the first sign of grade 1 ICANS.
Word-Finding Difficulty (Aphasia)
Slowed speech, inability to recall words, or pausing mid-sentence. Can progress to expressive aphasia at higher grades.
Handwriting Deterioration
The ICE score (Immune Effector Cell Encephalopathy) uses a simple handwriting sample as one of its five grading components. Worsening handwriting is an objective bedside sign.
Tremor and Seizure
Fine tremor may precede overt seizure. New-onset seizure at any grade requires urgent neurology review. All patients receive levetiracetam prophylaxis to reduce this risk.
ASTCT ICANS Grading Scale (Grades 1โ4)
The ASTCT 2019 consensus grading uses the ICE score plus level of consciousness, seizure activity, and signs of cerebral oedema to assign grade 1โ4.
| Grade | ICE Score | Consciousness | Seizure / Motor | Cerebral Oedema |
|---|---|---|---|---|
| Grade 1 | 7โ9 / 10 | Awakens spontaneously | None | None |
| Grade 2 | 3โ6 / 10 | Awakens to voice | None | None |
| Grade 3 | 0โ2 / 10 | Awakens to tactile stimulus | Any seizure, focal motor deficit | Localised on imaging |
| Grade 4 | 0 / 10 (unarousable) | Unarousable | Life-threatening prolonged seizure | Diffuse cerebral oedema |
ICANS Management Protocol at Indian CAR-T Centres
Indian CAR-T centres follow a structured escalation protocol based on ASTCT grade. All patients receive prophylaxis regardless of grade.
- 1
Universal Prophylaxis (All Patients)
Levetiracetam 500โ1000 mg BD commenced before CAR-T infusion and continued for a minimum of 30 days post-infusion, irrespective of ICANS development.
- 2
Grade 1 โ Observation and ICE Monitoring
Frequent ICE score assessment (every 8โ12 hours), neurology nursing review, no steroids at grade 1 unless symptoms progress rapidly.
- 3
Grade 2 โ Dexamethasone 10 mg IV q6h
Dexamethasone 10 mg intravenous every 6 hours, continued until ICANS improves to grade 1 or below, then taper over 3โ5 days. Neurology consult recommended.
- 4
Grade 3 โ High-Dose Dexamethasone + Neurology Consult
Escalate dexamethasone to 20 mg IV q6h. Mandatory neurology consult. MRI brain to exclude cerebral oedema. ICU monitoring if not already in place.
- 5
Grade 4 โ ICU with Cerebral Oedema Management
Intensive care admission. Methylprednisolone 1 g/day. Anti-oedema measures (mannitol, hypertonic saline). Anaesthesia involvement for ventilatory support if needed. Rare with NexCAR19.
ICANS Incidence โ NexCAR19 vs axi-cel
Pivotal trial data comparing neurotoxicity burden between NexCAR19 and the FDA-approved axi-cel benchmark.
- 15%Any-Grade ICANS โ NexCAR19Reported in the ImmunoACT pivotal trial across relapsed/refractory B-cell malignancies.
- 0%Grade 4 ICANS โ NexCAR19No grade 4 neurotoxicity events in the pivotal trial โ a key differentiator for international patients.
- ~64%Any-Grade ICANS โ axi-cel (ZUMA-1)Reported in the ZUMA-1 registration trial; 28% grade 3โ4. Context for the NexCAR19 safety advantage.
- 1โ2 weeksMedian Recovery Time (Grade 1โ2)Most ICANS grade 1โ2 events with NexCAR19 resolved within 1โ2 weeks with or without steroid intervention.
Neurology Support at Indian CAR-T Centres
Access to inpatient neurology consultation is an essential component of a functioning CAR-T programme. The three primary NexCAR19 centres in India each have different neurology infrastructure.
Tata Memorial Centre (TMC), Mumbai
Dr Vikram Bhalerao and the neurology team at TMC provide dedicated on-call coverage for haematology-oncology patients including CAR-T cases. TMC is the highest-volume NexCAR19 centre in India.
Apollo Hospitals
Apollo's dedicated neuro-oncology department at Chennai and Hyderabad provides full CAR-T neurotoxicity support. Apollo offers Kymriah (tisagenlecleucel) in addition to NexCAR19.
AIIMS New Delhi
Academic neurology department with direct integration into the haematology CAR-T programme. AIIMS provides specialist coverage including EEG, MRI, and CSF analysis for grade 3โ4 cases.
Long-Term Cognitive Effects
Long-term cognitive impairment after NexCAR19 is rare. Published data from ImmunoACT follow-up show no clinically significant cognitive decline at 6-month assessment in grade 1โ2 ICANS survivors.
More from the CAR-T India Resource Library
Continue exploring CAR-T care in India โ from the main programme overview to related side-effect management and treatment timelines.
Frequently Asked Questions โ ICANS and CAR-T in India
Is ICANS dangerous with NexCAR19?
Grade 1โ2 ICANS with NexCAR19 is generally manageable and resolves within 1โ2 weeks. The pivotal trial reported zero grade 4 events, which is the life-threatening category associated with severe cerebral oedema. This makes NexCAR19 one of the safer CAR-T products by neurotoxicity profile.
Will I be in hospital if ICANS develops?
Yes. All CAR-T patients are observed as inpatients for at least 7โ10 days post-infusion specifically to monitor for both CRS and ICANS. If ICANS develops, the hospital stay will be extended until neurological symptoms resolve to grade 1 or better.
Does dexamethasone affect CAR-T efficacy?
Short-course steroids for ICANS management are not believed to substantially compromise CAR-T efficacy based on current evidence. Prolonged high-dose steroids can suppress T-cell function; however, the brief dexamethasone courses used for grade 2โ3 ICANS are considered acceptable. This is different from CRS management where tocilizumab is preferred precisely to avoid this concern.
Can my family caregiver recognise ICANS early?
Yes โ and this is important. Caregivers are trained by the nursing team to watch for confusion, word-finding difficulty, and handwriting changes before discharge from close monitoring. A simple daily handwriting test (writing a sentence) is one practical bedside tool. Any new neurological symptom should be reported immediately to the treating team.
How CancerFax Helps
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