Abstract Details

Title Validation of the Chimeric Antigen Receptor (CAR) T-cell Therapy Neurotoxicity: A Single Center Study

Topic Neuro-oncology

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 4-006

Background

Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy comprised of genetically engineered T cells aimed at heightening the patient’s own immune system. Neurotoxicity (NT), commonly referred to as immune effector cell-associated neurotoxicity syndrome (ICANS), is a common complication of CAR T-cell therapy. An abbreviated MMSE bedside exam was developed for the early identification of ICANS and has been widely adopted. The CAR-T-cell-therapy-associated TOXicity (CARTOX)-10 screens for specific deficits in writing, attention, orientation, and naming and was later refined to the immune effector encephalopathy (ICE) assessment. However, there is little data validating the utility of the individual components of the bedside neurologic exam.

Objective

To validate the components of the CAR T-cell therapy bedside neurologic exam.

Design/Methods We performed a retrospective study on 26 adult relapsed/refractory diffuse large B-cell lymphoma patients treated with commercial CAR T-cell therapy (December 2017-September 2018).

Results NT of any grade and severe NT occurred in 88% (23/26) and 31% (8/26) of patients, respectively. Lower average CARTOX-10 score (p=<0.01), dysgraphia (p<0.01), disorientation (p=0.01), and inattention (p=0.018) were associated with severe NT, with positive predictive values of 100%, 87.5%, and 87.5%, respectively. Dysnomia was not associated with severe NT. Dysgraphia was a first presenting symptom in 40% (6/15) of non-severe NT patients (Day 3-18) and 88% (7/8) of severe NT patients (Day 0-9). A trend towards significance was observed between tremor and severe NT (p=0.08). All patients with severe NT had both dysgraphia and tremor 100% (8/8).

Conclusions In our limited cohort, the CARTOX-10 score is a reliable and useful tool to identify the emergence of severe NT. Dysgraphia, inattention, and disorientation are heralding signs of severe NT with high predictive values. Dysgraphia was the most common earliest presenting symptom in patients with severe CAR T-cell neurotoxicity, and was likely motor dysgraphia rather than a component of expressive aphasia.

Authors/Disclosures
Carlen A. Yuen, MD (University of California, Irvine) PRESENTER	Dr. Yuen 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.
Thomas J. Kelly, MD (Univ Of Chicago Dept Of Neurology)	No disclosure on file
	No disclosure on file