Neurologic Immune Related Adverse Events (Iraes) In Patients Treated With Immune Checkpoint Blockade.

3084 Background: Neurologic irAEs are uncommon but potentially fatal toxicities of immune checkpoint blockade (ICB). Their incidence, clinical and pathologic features, and association with therapy received are poorly understood. Methods: An IRB approved retrospective study was conducted to identify neurologic irAEs of all patients (pts) treated with ICB (anti-CTLA4, anti-PD1, anti-PDL1 monotherapy or in combination) from January 2010 to August 2017 at our institution. Clinical, radiologic, and pathologic features of neurotoxicity were collected. We excluded pts with primary CNS tumors or neurologic symptoms that were attributable to their CNS disease. Results: Of 4,864 pts who received anti-CTLA4, anti-PD1, or anti-PDL1 either as monotherapy or in combination, neurologic irAEs developed in 81 (1.67%; 95% CI, 1.34% to 2.06%). Clinical, radiographic, and radiologic features of neurotoxicity were diverse. Time to onset ranged from 3 days to 17 months with a median of 2 doses (1 to 20) received. The incidence was higher with combination therapy versus monotherapy (36 of 1,448 [2.49%] v 45 of 3416 [1.32%]; P = 0.0047), and there was no significant difference in incidence among patients age ≤ 65 at time of treatment versus patients age > 65 (41 of 2,705 [1.90%] v 40 of 2,159 [1.85%]; P = 0.3692). Of pts who experienced neurotoxicity, 60% (49 of 81) were hospitalized, 5 (10%) in the ICU. Fifty nine percent (48 of 81) had a concurrent non-neurologic irAEs. Sixty nine percent (56 of 81) had grade 1-2 neurologic events and 77% (63 of 81) improved/resolved with drug holding/immunosuppression. Eight patients worsened clinically or died during the course of neurotoxicity treatment. Conclusions: Neurologic irAEs have variable clinical presentation and are more common when anti-CTLA-4 or anti-PD1/PD-L1 mAbs are combined with each other or with other checkpoint inhibitors. Incidence is similar among pts of advanced age and younger pts. Most events improve/resolve with drug holding/immunosuppression, but pts may require hospitalization and experience worsening despite immunosuppression. This underscores the need for earlier identification, as patient outcomes may improve with earlier treatment.