Multicenter, Real-World Study in Patients with R/R Large B-Cell Lymphoma (LBCL) Who Received Lisocabtagene Maraleucel (liso-cel) in the United States (US)

Background Liso-cel is an autologous, CD19-directed, 4-1BB CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells with demonstrated efficacy and favorable safety in clinical studies. We report real-world postmarketing data of commercial liso-cel in patients with R/R LBCL using data collected at the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods This is a noninterventional, observational, multicenter study of US patients followed in the CIBMTR Cellular Therapy Registry between Feb 2021 and Nov 2022 after infusion with commercial liso-cel (conforming product only) for treatment of R/R LBCL. Outcomes included ORR, CR, duration of response (DOR), PFS, OS, and risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Results At data cutoff (May 4, 2023), 323 patients who received commercial liso-cel across 54 treatment sites were included in the analysis (see Table for baseline characteristics). Median (IQR) time from leukapheresis to liso-cel infusion was 36 d (34–42). Median number of prior lines of systemic therapy was 3, with 25% of patients having received ≥ 4 lines. Median (range) time from diagnosis to liso-cel infusion was 1.4 y (0.2–29.7). At a median follow-up of 7.4 mo, ORR was 79%, with a CR rate of 65%. Median (IQR) time to response was 1.2 mo (1.0–3.1). Median DOR was not reached; DOR rate at 6 mo was 73% (95% CI, 66%–79%). Median PFS and OS were not reached at data cutoff. Estimated 6-mo PFS and OS rates were 64% and 82%, respectively. Most CRS and ICANS events were low grade, with no CRS and ICANS reported in 48% and 70% of patients, respectively; 52% of patients had CRS and 3% had grade ≥ 3 events. The most common treatments for CRS were tocilizumab (20%) and corticosteroids/tocilizumab (12%). ICANS was seen in 30% of patients, with grade ≥ 3 events in 11%. ICANS was mostly treated with corticosteroids (12%) and corticosteroids/antiepileptics (5%). Grade 5 CRS and ICANS were observed in 3 and 3 patients, respectively, and all but 2 patients had concomitant causes of death (disease progression [n = 3], hemophagocytic lymphohistiocytosis [n = 2]). Prolonged cytopenia (grade 4 thrombocytopenia and/or neutropenia 30 days after infusion) occurred in 10% of patients. Conclusions This is the first large, multicenter, real-world study of patients with R/R LBCL who received commercial liso-cel in the US. Baseline characteristics of these patients showed a broader patient population than those eligible for the liso-cel registrational study. One-time infusion of liso-cel showed deep and durable responses in patients with R/R LBCL across a broad age range, including those with high-risk disease features. Incidence of severe (grade ≥ 3) CRS and ICANS was low. These results further support liso-cel as a therapeutic option for a broad, real-world population of patients with R/R LBCL.