Abstract Details

Title CAR-T Cell Therapy in Recurrent Primary CNS Lymphoma (PCNSL): A Phase 2 Clinical Trial

Topic Neuro-oncology

Presentation(s) S27 - Innovations in Neuro-oncology (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

Background Relapsed or recurrent (r/r) PCNSL is a challenging condition with overall poor prognosis. CAR-T cell therapies have emerged as a powerful treatment for r/r hematological malignancies. However, due to heightened concerns of neurotoxicity, patients with PCNSL were excluded from all pivotal CAR-T studies.

Objective To evaluate safety and efficacy of Tisagenlecleucel in recurrent or relapsed PCNSL.

Design/Methods We conducted a phase 2 study of CD-19 targeted tisagenlecleucel in adults with r/r PCNSL (NCT04134117). The primary endpoint was safety and tolerability including assessment for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Secondary endpoints included overall response rate (ORR) and complete response (CR) rate. Exploratory endpoints included expansion, persistence and phenotype of tisagenlecleucel, cytokine profiling of blood and CSF and CNS trafficking of CAR-T cells.

Results 10 subjects were enrolled and 9 were infused with a median age of 67 years (range, 34-81). All patients had progressed after first line high-dose methotrexate and received a median of 4 prior lines of therapy. Grade 1 CRS was observed in 6 patients (median onset of 4 days; range, 1-5). ICANS developed in 5/9 patients (median time of onset of 5 days; range, 3-11), including only one patient with grade 3 ICANS. 5/9 patients (55.6%) achieved a CR. With a median follow-up of 7.4 months for survivors, 6/9 patients were alive with 4/9 (44.4%) showing sustained responses.

Conclusions Tisagenlecleucel in r/r PCNSL was efficacious with manageable toxicity. The majority of patients in this heavily pretreated population showed a response, including responses beyond 12 months. Tisagenlecleucel was found to expand in the peripheral blood and CNS with CSF gene signatures suggestive of higher CAR-T cell infiltrates in responding patients

Authors/Disclosures
Jorg Dietrich, MD, PhD, FAAN (Massachusetts General Hospital, Harvard Medical School) 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 publishing royalties from a publication relating to health care.
Yi-Bin Chen	No disclosure on file
	No disclosure on file
Justin T. Jordan, MD, MPH, FAAN (Massachusetts General Hospital)	Dr. Jordan has received personal compensation for serving as an employee of City of Beverly. An immediate family member of Dr. Jordan has received personal compensation for serving as an employee of Dietitians on Demand. An immediate family member of Dr. Jordan has received personal compensation for serving as an employee of Genesis HR Solutions. An immediate family member of Dr. Jordan has received personal compensation for serving as an employee of Harborlight Montesorri. Dr. Jordan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Navio Theragnostics. Dr. Jordan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Recursion Pharmaceuticals, Inc. Dr. Jordan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BCD Meetings. Dr. Jordan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Shepherd Therapeutics. Dr. Jordan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Jordan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akeila Bio. Dr. Jordan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springworks Therapeutics. Dr. Jordan has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Continental Casualty Company. Dr. Jordan has stock in Navio Theragnostics. Dr. Jordan has stock in The Doctor Lounge. An immediate family member of Dr. Jordan has stock in OldGate. Dr. Jordan has stock in Akeila Bio. The institution of Dr. Jordan has received research support from NIH. The institution of Dr. Jordan has received research support from Department of Defense. The institution of Dr. Jordan has received research support from PCORI. Dr. Jordan has received publishing royalties from a publication relating to health care. Dr. Jordan has received personal compensation in the range of $500-$4,999 for serving as a Reimbursement for potential consultant role that was aborted with Magnet Biomedicine. Dr. Jordan has a non-compensated relationship as a board member with United Council for Neurologic Subspecialties that is relevant to AAN interests or activities.
Deborah Forst, MD	Dr. Forst has stock in Eli Lilly. Dr. Forst has received research support from Conquer Cancer Foundation of the American Society of Clinical Oncology. Dr. Forst has received research support from Palliative Care Research Cooperative Group. Dr. Forst has received research support from American Cancer Society Institutional Research Grant.
Scott R. Plotkin, MD, PhD, FAAN (Mass General Cancer Center)	Dr. Plotkin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NFlection Therapeutics. Dr. Plotkin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Akouos. Dr. Plotkin has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SonALAsense. Dr. Plotkin has stock in NFlection Therapeutics. Dr. Plotkin has stock in NF2 Therapeutics. Dr. Plotkin has stock in SonALAsense. Dr. Plotkin has received research support from Children's Tumor Foundation. Dr. Plotkin has received research support from Department of Defense. Dr. Plotkin has received research support from National Institutes of Health. Dr. Plotkin has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Tracy T. Batchelor, MD, MPH (Brigham and Women's Hospital)	Dr. Batchelor has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Up To Date, Inc. An immediate family member of Dr. Batchelor has received publishing royalties from a publication relating to health care. Dr. Batchelor has received publishing royalties from a publication relating to health care.
	No disclosure on file
Matthew Frigault	No disclosure on file