ABCL-044 Clinical Outcomes of Commercial CD19-Targeted CAR T-Cell Therapy in Patients With Secondary Central Nervous System Lymphoma

Abstract

We hypothesized that CD19-targeted chimeric antigen receptor (CAR) T-cell therapy is safe and feasible among high-grade B cell lymphoma (HGBCL) patients with secondary central nervous system (CNS) lymphoma. To evaluate the safety and efficacy of CD19-targeted CAR T-cell therapy in patients with relapsed/refractory HGBCL with secondary CNS lymphoma involvement. Patients who had active CNS involvement at the time of CAR T-cell therapy were identified retrospectively in a single-institution database of 101 consecutive HGBCL patients who received either tisagenlecleucel (tisa-cel) or axicabtagene ciloleucel (axi-cel) between 2017 and 2021. The best overall post-CAR T-cell therapy response was defined as the lowest disease burden measured at any time between post-CAR T-cell therapy and additional salvage therapies. Survival analysis was conducted using the Kaplan-Meier method. Overall, 19 HGBCL patients with active secondary CNS lymphoma (5 parenchymal, 9 leptomeningeal/CSF, 5 parenchymal and leptomeningeal) were identified, with a median age of 59 years (16-79 years) at the time of apheresis. All patients in the cohort received tisa-cel with a pre-conditioning regimen of fludarabine and cyclophosphamide. The median follow-up was 5.2 months (range, 0.8-36.8 months) from the date of CAR T-cell infusion. Ten patients had concurrent systemic involvement at the time of infusion. Seventeen patients received bridging therapy, of whom four received radiation therapy (patients/radiation field: 2/craniospinal, 1/whole brain, 1/skull base). Cytokine release syndrome occurred in 16 patients, among whom no grade 3 or higher event was reported. Neurotoxicity syndrome occurred in 9 patients, one of whom reported a grade 4 event. The best objective CNS response (complete response and partial response) rate post-CAR T infusion as per MRI was 58% (n=11): parenchymal (n=3, 60%), leptomeningeal/CSF (n=5, 56%), parenchymal and leptomeningeal (n=3, 60%). The median overall survival and progression-free survival from the start of CAR T-cell therapy were 12.7 months (95% CI: 5.4 months-not reached) and 3.9 months (95% CI: 0.93 months-not reached), respectively. Our data demonstrate that CD19-targeted CAR T-cell therapy is safe and feasible among HGBCL patients with secondary CNS lymphoma. Prospective cohort studies are required for validation.