CAR-T-cell-Related Encephalopathy Syndrome: High Rates of Neurotoxicity in Clinical Practice (P1.6-007)

Objective: To describe clinical features of Chimeric Antigen Receptor T cell (CAR-T-cell) Related Encephalopathy Syndrome (CRES) to better understand the clinical features to potentially permit instituting earlier treatment and supportive care. Background: CRES is a known adverse event associated with CAR-T-cell therapy. Predictive modeling is essential for early identification and prevention of severe CRES. Design/Methods: In this retrospective study, 26 patients with relapsed refractory diffuse large B cell lymphoma (DLBCL) who received commercial CAR-T cell therapy (25 axicabtagene ciloleucel [Yescarta®], 1 tisagenlecleucel [Kymriah®]) were assessed for CRES (CTCAE criteria), increased intracranial pressure (ICP), CSF abnormalities, CNS endothelial compromise, seizures and encephalopathy. Results: Twenty-three patients developed CRES of any grade (I 43%, II 22%, III 17%, IV 17%). On average, CRES developed on Day 6 after CAR-T infusion (ranging from Day 1 to 13), resolving between 1 day to remaining unresolved. Death from disease progression occurred in 15%. Older age (average age 61 vs 52), male gender (65%), psychosis (9%), exclusive dysgraphia (22%), elevated OP (>20mmHg, 23%), and triphasic waves (25% of EEGs), were associated with severe (Grade III and IV) CRES. Tremulousness was the most common first sign of neurotoxicity (74%), followed by dysgraphia (61%), disorientation (48%), dyscalculia (48%), and dysnomia (30%). Headache (74%) was noted in CRES of all grades. Of 13 who received lumbar punctures, 77% had lymphocytic pleocytosis and 85% had elevated protein. Of 12 patients who obtained EEG, findings of encephalopathy (75%), and Frontal Intermittent Rhythmic Delta Activity (17%) were noted. Of 13 who had brain MRI wwo, none showed enhancement. Abnormal average CARTOX-10 scores (Neelapu et al. 2017) were CRES Grade I 9.9, II 7.8, III 5.5, IV 4.9. Conclusions: Off-protocol CAR-T for DLBCL results in a high frequency of CRES and heterogeneous presentations. Most patients recover. Additional studies on the value of baseline predictors are warranted. Disclosure: Dr. Yuen has nothing to disclose. Dr. Wu has nothing to disclose. Dr. Reder has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Bayer, Genzyme, Genentech. Dr. Reder has received personal compensation in an editorial capacity for Medlink. Dr. Reder has received research support from Biogen, Novartis, Bayer, Malinkrodt, Serono, Genentech. Dr. Rezania has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Mitsubishi, Tanabe, Alnylam. Dr. Rezania has received royalty, license fees, or contractual rights payments from Medlink, AANEM. Dr. Soliven has nothing to disclose. Dr. Mastrianni has nothing to disclose. Dr. Xie has nothing to disclose. Dr. Artz has received research support from Miltenyi Biotech. Dr. Kosuri has nothing to disclose. Dr. Riedell has received research support from Lymphoma Research Foundation. Dr. Park has received research support from NIH. Mr. Bishop has nothing to disclose.