Abstract Details

Title Neurotoxicity as Surrogate Marker for CAR T-cell Therapy Treatment Response

Topic Neuro-oncology

Presentation(s) P2 - Poster Session 2 (8:00 AM-9:00 AM)

Poster/Presentation
Number 13-006

Objective To analysts CAR T-cell therapy neurotoxicity (NT) as a potential surrogate marker for response to CAR T-cell therapy and as an indicator of a robust therapeutic response.

Background

CAR T-cell therapy is a novel immunotherapy comprised of genetically engineered T cells aimed at heightening the patient’s own immune system.

Immune-related adverse events are commonly reported with CTLA-4, PD-1 and PD-L1 checkpoint inhibitors and are significantly associated with increased OS and PFS. Adverse events coupled to a robust inflammatory/immune response is also reminiscent of IRIS in AIDS patients following HAART, in which paradoxical unmasking of prior subclinical infections arise as the immune system is restored.

Design/Methods

A retrospective chart review was performed for 26 patients with relapsed or refractory DLBCL who received CAR T-cell therapy between December 2017 and September 2018. Medical records were reviewed for baseline demographics, CAR T-cell treatment, response to cellular therapy, incidence and severity of NT, and outcomes.

Results In this cohort, 23/26 (88%) patients who received CAR T-cell therapy developed NT; 8/26 (31%) were severe (Grade III-IV by CTCAE). Severe NT was associated with achieving a complete remission compared to progressive disease at 3 months post infusion by both CTCAE (2.4 ±1.1 vs. 1.4 ± 1.3, p = 0.051) and CARTOX-10 (8.3 ± 1.6 vs. 9.4 ± 1.5, p = 0.038) grading systems. However, NT severity was not significantly associated with overall survival by either CTCAE score (9 ±1.5 vs. 8.8 ±1.9, p = 0.787) or CARTOX-10 scores (1.87 ±1.19 vs. 2.11 ±1.45, p = 0.741). Death occurred in 6/26 (23%) patients, as a result of disease progression (n = 5) or cardiac arrest (n = 1), not NT.

Conclusions

Paradoxically, NT severity is positively correlated with a statistically significant improvement in progression-free survival in off-protocol CAR T-cell therapy, and may therefore indicate an effective therapeutic response.

Authors/Disclosures
Carlen A. Yuen, MD (University of California, Irvine) PRESENTER	Dr. Yuen has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Thomas J. Kelly, MD (Univ Of Chicago Dept Of Neurology)	No disclosure on file
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, F�鶹��ýӳ�� (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.
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.
Ali Saad, MD, F�鶹��ýӳ��	Dr. Saad has nothing to disclose.
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.
Deric M. Park, MD (University of Virginia)	No disclosure on file
	No disclosure on file
	No disclosure on file

�鶹��ýӳ��

�鶹��ýӳ��