Abstract Details

Title CAR-T-cell-Related Encephalopathy Syndrome: High Rates of Neurotoxicity in Clinical Practice

Topic Neuro-oncology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-007

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.

Authors/Disclosures
Carlen A. Yuen, MD (University of California, Irvine) PRESENTER	Dr. Yuen has nothing to disclose.
Shasha Wu, MD, PhD (University of Chicago)	Dr. Wu has nothing to disclose.
Anthony Reder, MD (University of Chicago)	Dr. Reder has nothing to disclose.
Kourosh Rezania, MD, FAAN (University of Chicago)	Dr. Rezania has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Akcea. Dr. Rezania has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alnylam.
Betty C. Soliven, MD (University of Chicago)	Dr. Soliven has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CVS Pharmacy. The institution of Dr. Soliven has received research support from NIH. The institution of Dr. Soliven has received research support from NIH. The institution of Dr. Soliven has received research support from Alexion. The institution of Dr. Soliven has received research support from Roche/Genentech.
James A. Mastrianni, MD, PhD (University of Chicago)	Dr. Mastrianni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CVS Caremark. Dr. Mastrianni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Mastrianni has received research support from Brain Research Foundation.
Tao Xie, MD (University of Chicago)	Dr. Xie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CVS/Caremark. Dr. Xie has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharmaceutical Ltd. Dr. Xie has received research support from NIH.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Deric M. Park, MD (University of Virginia)	No disclosure on file
Michael Bishop (��ɫ��)	No disclosure on file

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