Outcomes of Large B-Cell Lymphoma (LBCL) Patients with Secondary Central Nervous System Involvement Following Chimeric Antigen Receptor T-Cell Therapy: A CIBMTR Analysis

Background Chimeric antigen receptor T-cell (CAR-T) therapy is a standard treatment option for patients (pts) with relapsed and refractory large B cell lymphoma (LBCL). Outcomes in pts with LBCL with secondary CNS involvement (SCNSL) are poor and treatment options are limited. There are limited data on the outcomes of SCNSL with CAR-T. In this study, we describe the efficacy and safety of CAR-T in SCNSL pts reported to the CIBMTR registry. Methods All adult pts in the CIBMTR registry receiving CD19-direct commercial CAR-T infusion for SCNSL from June 2015 to March 2022 were included. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), relapse/progression, cytokine-release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and non-relapse mortality (NRM). Multivariate analysis was performed to determine factors affecting OS and PFS. Results A total of 144 pts from 52 centers were included in the analysis. Pt demographics are highlighted in Table 1. Median follow up was 24 (2-52) months. The median (range) age at time of CAR-T infusion was 61 years (23–83) with 35% of the pts ≥65 years. Twelve percent had KPS score <60. With a median of 3 (1-9) prior lines of therapy, 42% had primary refractory disease and 84% had early treatment failure. 56% of the pts received bridging therapy (48% chemotherapy, 5% intrathecal/ intraocular therapy, and 3% radiation therapy) prior to receiving CAR-T.The 2-year PFS and OS were 21% (95% CI 15-29) and 34% (95% CI 25-43), respectively. Incidence of any grade CRS and ICANS was 75% and 35%, respectively, with grade ≥3 CRS and ICANS seen in 12% and 24% of the pts, respectively. Median time (range) to onset of CRS and ICANS were 4 (1-10) and 6 (1-33) days, respectively. 90% (95% CI 85-95) of the pts had neutrophil count recovery by 1 month and 82% (95% CI 76-82) of the pts had platelet count recovery by 100 days post CAR-T. The 2-year cumulative incidence of relapse/progression and NRM were 74% (95% CI 66-81) and 5% (95%CI 1.8-9.8), respectively. In multivariable analysis, KPS <90% was the only factor associated with inferior OS (hazard ratio 2.23, 95% CI 1.3-3.8) (Figures 1 and 2). Recurrence/persistence/progression of the primary disease was the most common (81%) cause of death. Conclusion This is the largest real-world analysis to date evaluating outcomes in pts with SCNSL treated with CAR-T. Although increased CAR-T related toxicity was not observed when compared to LBCL without SCNS involvement, pts with SCNSL had very high rates of progression and low rates of PFS with currently available CAR-T-cell therapies.