Background: No clinical studies have yet evaluated CAR T cell therapies in pts with R/R B-cell NHL who have secondary CNS lymphoma. We report data from this pt subgroup receiving liso-cel (JCAR017), an investigational, anti-CD19 CAR T cell product administered as a defined composition of CD4+/CD8+ CAR T cells, in the phase 1 TRANSCEND NHL 001 study. Methods: Eligible pts had confirmed B-cell NHL with R/R disease after ≥2 prior lines of therapy. Pts with secondary CNS lymphoma could enroll or, if it developed on study, could continue to receive liso-cel. After lymphodepleting chemotherapy, liso-cel was administered at 1 of 2 dose levels (DL): DL1 = 50 × 10⁶ or DL2 = 100 × 10⁶ total CAR+ T cells. Efficacy was evaluated per the Lugano criteria. Pts achieving a complete response could be retreated with liso-cel upon progressive disease. Results: At data cutoff, 9 pts with secondary CNS lymphoma at initial treatment (n = 6), retreatment (n = 2), or cycle 2 (n = 1) received liso-cel. 4 pts were treated at DL1 and 5 at DL2. The median (range) age was 60 (47‒73) years and number of prior lines of therapy was 3 (2‒7). Median time to peak CAR+ T cell expansion was 12.5 (7–112) days. 1 of 9 pts had grade (G)2 cytokine release syndrome (CRS) and 1 of 9 pts had a neurological event (NE; G3 decreased level of consciousness). No retreatment pts had CRS or NE; however, 1 retreatment pt had an NE of G2 temporal edema with initial treatment with liso-cel. 5 pts received prophylactic levetiracetam. 1 pt received corticosteroids and tocilizumab. Other toxicities were predominantly cytopenias. There were no treatment-related deaths. 4 pts responded to liso-cel; all had a best response of complete response, of which 2 are ongoing at 270 and 545 days post-liso-cel. All 4 responses occurred after initial liso-cel treatment; no retreated pts responded. Conclusions: In the ongoing TRANSCEND NHL 001 study, liso-cel continues to demonstrate the ability to be safely delivered to pts with R/R B-cell NHL, including those with secondary CNS lymphoma, a population of pts with a highly unmet medical need. No excess NE was noted in this population. This cohort continues to be evaluated. Clinical trial information: NCT02631044