CTIM-37. A PILOT STUDY OF AXICABTAGENE CILOLEUCEL (AXI-CEL) FOR THE TREATMENT OF RELAPSED/REFRACTORY PRIMARY AND SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL AND SCNSL)

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 25; no. Supplement_5; p. v71
• Main Authors: Nayak, Lakshmi, Falvey, Caroline, Bouvier, Riemke, Chukwueke, Ugonma, Hogan, Sarah, Kendricken, Elizabeth, Meehan, Christopher, Redd, Robert, Fisher, Jennifer, Torres, Alexandra, Jones, Julia, Lee, Eudocia, Kim, Austin, Castro, Luis Nicolas Gonzalez, McFaline-Figueroa, Jose Ricardo, Aquilanti, Elisa, Youssef, Gilbert, Arrillaga-Romany, Isabel, Murakami, Mark, Sholl, Lynette, Meredith, David, Huang, Raymond Y, Ramsdell, Linda, Gerdemann, Ulrike, Keskula, Paula, Kaminski, Jim, Albanese, Alexandre, Bi, Wenya Linda, Arnaout, Omar, Reardon, David, Wen, Patrick, Poddar, Soumya, Mao, Daqin, Mattie, Mike, Davis, Madison, Filosto, Simone, Kean, Leslie, Armand, Philippe, Jacobson, Caron
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 10.11.2023
• Subjects: Clinical Trials: Immunologic
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noad179.0277

Abstract BACKGROUND Optimal therapy for patients with relapsed/refractory (R/R) CNSL is not defined, and their prognosis is poor. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel(axi-cel) has demonstrated superior efficacy over standard of care in R/R systemic diffuse large B-cell lymphoma and could be an effective regimen for R/R CNSL. METHODS This is a pilot study of axi-cel in patients with R/R CNSL. Only corticosteroids were allowed for bridging. Patients underwent lymphodepletion with fludarabine and cyclophosphamide followed by standard axi-cel dosing of 2x106 cells/kg infusion. An Ommaya reservoir was placed prior to infusion. The first 6 patients enrolled were observed for treatment-limiting toxicities(TLTs). The study enrolled a total of 17 patients. Primary endpoint was safety, measured by rate of TLTs and grade 3+ adverse events(AEs). Secondary endpoints included objective response rate(ORR), complete response(CR) rate, duration of response(DOR), progression-free survival(PFS) and overall survival(OS). Exploratory analyses included paired peripheral blood and CSF analyses for axi-cel pharmacokinetics, cytokine levels, flow cytometry, single-cell RNA-Seq and circulating tumor-DNA. RESULTS We report the results of all 17 patients(13 PCNSL, 4 SCNSL) enrolled. Median age was 64 years (34-80), 8/17 were women. As of 6/2023, 14 treated patients had >1 month follow-up, with 86%(12/14) ORR and 64%(9/14) CR. Six patients progressed. No TLTs were observed; 15/16(94%) patients developed cytokine release syndrome/CRS (grade 3+, 0%), 8/16(50%) developed immune effector cell-associated neurologic syndrome/ICANS, (grade 3+, 5/16(31%)). PFS, OS, DOR and correlatives will be reported at the meeting. Daily examination of CAR T-cells in blood and CSF by scRNA-Seq revealed evolution of a prominent Type I interferon (IFN) transcriptomic signature of CAR-Ts in the CSF. CONCLUSION Axi-cel is safe and well-tolerated in CNSL patients with promising efficacy and no apparent additional risk of adverse neurologic events including ICANS. IFN pathway may play a major role in CAR-T efficacy in CNSL.