Abstract Details

Title Toxicities and Outcome after CD19-directed Chimeric Antigen Receptor T-cell Therapy for Neurolymphomatosis

Topic Neuro-oncology

Presentation(s) S29 - Neuro-oncology (5:18 PM-5:30 PM)

Poster/Presentation
Number 010

Objective To describe toxicities and outcome after CD19-directed Chimeric Antigen Receptor T-cell Therapy for Neurolymphomatosis.

Background Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis.

Design/Methods Observational cohort study. Neurolymphomatosis patients treated with CD19 CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification, management, and response rates were recorded.

Results Eleven neurolymphomatosis cases with a median of 2 lines of treatments (range: 1-3) prior to CD19-CAR T-cells were identified. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome was detected in 8/11 (73%; grade 1: N = 7; grade 2: N =1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions were achieved in three cases (27%), of which two are still sustained now 9 and 46 months after CD19-CAR infusion. All radiographic responses were associated with remission of neurological symptoms.

Conclusions CD19-CAR T-cell treatment was well tolerated and yielded promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier, and toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.

Authors/Disclosures
Jorg Dietrich, MD, PhD, FAAN PRESENTER	Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Therapeutics. Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Johnson. Dr. Dietrich has received publishing royalties from a publication relating to health care.
Philipp Karschnia	Philipp Karschnia has nothing to disclose.
Sofia Doubrovinskaia (University of Heidelberg)	No disclosure on file
Wolfgang Wick	The institution of Wolfgang Wick has received research support from Roche. The institution of Wolfgang Wick has received research support from Pfizer. The institution of Wolfgang Wick has received research support from Apogenix.
Maria Martinez-Lage, MD (Massachusetts General Hospital)	The institution of Dr. Martinez-Lage has received research support from NIH.
Ganesh Shankar	Ganesh Shankar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Depuy. The institution of Ganesh Shankar has received research support from NuVasive.
Jeremy Abramson	Jeremy Abramson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS. Jeremy Abramson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Interius. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Seagen. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Jeremy Abramson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Jeremy Abramson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astra-Zeneca. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Jeremy Abramson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Foresight Diagnostics. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miltenyi Biotec. Jeremy Abramson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BeiGene. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. The institution of Jeremy Abramson has received research support from Allogene. The institution of Jeremy Abramson has received research support from BMS. The institution of Jeremy Abramson has received research support from Genentech. Jeremy Abramson has received research support from Cellectis. The institution of Jeremy Abramson has received research support from Merck.
Matthew Frigault	No disclosure on file
Leon D. Kaulen, MD	Dr. Kaulen has nothing to disclose.

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