Neurotoxicity in phase 2 trial
The incidence of neurotoxicity in the ELIANA trial was 30 of 75 patients
(40%) within 8 weeks after infusion. Ten patients had grade 3
neurologic events, but no grade 4 events or cerebral edema were
reported. The majority of neurologic events occurred during CRS or
shortly after its resolution. Severe neurologic events occurred more
frequently in patients with higher-grade CRS (grade 3 neurologic events
occurred more frequently in patients with grade 4 CRS than among those
with grade 0 through 3 (32% vs. 7%; 95% CI for the difference, -1 to
50 percentage points)). Among grade 3 neurologic episodes that resolved,
50% resolved within 10 days, and 75% resolved within 18 days21. Interestingly, neurotoxicity does not appear to be
correlated with CNS involvement, as 3 of 17 patients (18%) with CNS
disease compared to 12 of 43 patients (28%) without CNS disease
developed encephalopathy in CTL019 trial 39. The
grading for ICANS has now also been presented in the ASTCT consensus
paper 34. This scale now provides consistent grading
for encephalopathy as well as other major events such as seizures or
cerebral edema, while not including headache (very common in patients
with even mild CRS), or CNS hemorrhage, which is graded separately as a
bleeding event.