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.