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)

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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.