Real-World (RW) Outcomes of Lisocabtagene Maraleucel (liso-cel) in Patients (pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL) and Secondary Central Nervous System (sCNS) Involvement from the Center for International Blood and Marro

Background: Despite recent advances, management of R/R LBCL with sCNS involvement remains an unmet medical need due to poor survival and limited clinical trial enrollment and data. The primary objective of this study was to evaluate RW effectiveness and safety of liso-cel, an autologous, CD19-directed, 4-1BB CAR T cell product, in pts with R/R LBCL and sCNS involvement. Methods: This is an observational study of pts in the United States with R/R LBCL and sCNS involvement followed in the CIBMTR Cellular Therapy Registry between 02/2021 and 05/2024. Pts who had commercial liso-cel infusion and ≥ 1 postinfusion assessment for effectiveness and safety were included. Effectiveness outcomes included ORR, CR rate, duration of response (DOR), PFS, and OS. Safety outcomes included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), clinically significant infection rate, and prolonged cytopenia (grade 4 thrombocytopenia and/or neutropenia persistent at Day 30 after infusion). Results: At data cutoff (05/07/2024), among 36 pts across 19 centers, median age was 62 y (range, 30-83) and 56% of pts were male. Most (69%) pts had DLBCL (40% with activated B-cell type, 36% with germinal center B cell type, 24% with not otherwise specified), 25% had high-grade B-cell lymphoma, and 6% had other histologies. Of the 25 pts with DLBCL, 28% had transformed from CLL or other histologies. Sixteen pts had lesions at ≥ 2 sites, including non-CNS sites. Parenchymal lesions were reported in 30 (83%) pts, and nonparenchymal (cerebrospinal fluid, epidural, leptomeningeal) lesions in 6 (17%) pts, including 1 pt with lesions at multiple nonparenchymal sites; no pts had lesions in both sites. Among 31 pts with ECOG data, 13% had ECOG PS of 2 and none had ECOG PS of 3 or 4. Most pts (77%, 20/26 with available data) had ≥ 1 comorbidity, with cardiac (42%, 11/26) and pulmonary (31%, 8/26) being the most common. At the time of infusion, 97% of pts had active disease and 72% had refractory disease. The median (range) number of prior lines of therapy was 3 (1-13), and 9% (3/35) of pts had prior ASCT. Overall, 39% and 53% had received intrathecal and radiation therapy, respectively; 19% were previously exposed to Bruton tyrosine kinase inhibitors, an emerging therapeutic modality for sCNS in the RW setting. Among 32 pts with bridging data available (ie, yes or no), 81% had received bridging therapy. At a median (range) follow-up of 12 mo (1-24), ORR (95% CI) was 64% (46%-79%) and CR rate (95% CI) was 53% (36%-70%). The probability of DOR (95% CI) at 6 and 12 mo was 73% (46%-88%) and 55% (26%-76%), respectively. The probability of PFS (95% CI) at 6 and 12 mo was 48% (30%-64%) and 36% (17%-54%), respectively. The probability of OS (95% CI) at 6 and 12 mo was 64% (45%-78%) and 39% (20%-58%), respectively. CRS, mostly low grade, was reported in 64% of pts, and 53% did not experience any ICANS, with no grade 4 or 5 ICANS. Grade ≥ 3 CRS and ICANS were reported in 3 (8%) pts (no grade 3, 2 grade 4, and 1 grade 5 CRS) and 8 (22%) pts (all grade 3 events), respectively. Median time to onset and duration of CRS and ICANS were similar to those previously reported (Crombie JL, et al. ASH 2023; Presentation 104). The most common treatments were tocilizumab alone (28%) for CRS and corticosteroids alone (19%) or corticosteroids plus antiepileptics (14%) for ICANS. Prolonged cytopenia was reported in 25% of pts and clinically significant infections in 50% of pts, most of which were viral. There were no reported cases of second primary malignancies. For 17/19 (89%) deaths reported, the primary cause was progression of primary disease; cause was unknown or not reported for the other 2 cases. Two of the deaths occurred ≥ 30 d postinfusion, including the pt with grade 5 CRS; in both cases, disease progression was reported as the primary cause of death. Conclusions: These early results support the use of liso-cel as a feasible and effective therapeutic option in RW pts with R/R LBCL and sCNS involvement, a population with high unmet need and poor prognosis and survival. CR rate in this population was similar to that observed in the overall population in the TRANSCEND NHL 001 (NCT02631044) study despite all pts in this study having sCNS involvement. The safety profile of liso-cel in pts with sCNS was manageable and consistent with pivotal trials and prior RW reports; there were no new safety signals and no grade 4-5 ICANS in this high-risk population, despite sCNS involvement.