Efficacy and safety of lisocabtagene maraleucel monotherapy in relapsed or refractory large B-cell lymphoma: A systematic review and meta-analysis of clinical trials and real-world studies

Abstract Background: Relapsed or refractory (R/R) large B-cell lymphoma (LBCL) has historically been associated with limited responses to therapies beyond second-line salvage regimens, resulting in poor clinical outcomes. Lisocabtagene maraleucel (liso-cel), an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell therapy, is FDA-approved for the treatment of R/R LBCL. In clinical trials, it has demonstrated deep and durable responses with a favorable safety profile. While multiple CAR T-cell therapies are currently approved for the treatment of R/R LBCL, most existing meta-analyses pool data across CAR T-cell products, limiting product-specific conclusions. To address this, we conducted a systematic review and meta-analysis to characterize the efficacy and toxicities of liso-cel monotherapy in patients with R/R LBCL and to inform therapeutic decision-making with product-specific evidence. Methods: In this meta-analysis, PRISMA guidelines were followed and PubMed, Embase, and Cochrane databases were used to identify studies reporting efficacy and safety outcomes of liso-cel monotherapy in R/R LBCL. Study selection was performed independently by two authors, and any discrepancies were resolved by a third reviewer. A total of 11 studies (n = 1206 patients) were included, comprising five clinical trials and six retrospective real-world studies. Meta-analyses were performed using the R meta package. A random-effects model was applied. Heterogeneity was assessed using the I2 statistic. Outcome Measures: The primary endpoint of this meta-analysis was overall response rate (ORR). Secondary endpoints included complete response (CR), overall mortality rate (OMR), mortality due to disease progression, mortality due to adverse events, and the incidence of significant grade ≥ 3 adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Results: In total, five clinical trials and six real-world retrospective studies were pooled for analysis (n = 1206). The pooled ORR was 78% (95% confidence interval CI, 73%–82%) and CR was 60% (95% CI, 55%–66%). OMR was 38% (95% CI, 30%–46%). The pooled prevalences of mortality due to disease progression and due to adverse events were 28% (95% CI, 18%–38%) and 4% (95% CI, 3%–6%), respectively. Grade ≥ 3 hematologic adverse events were most common, including neutropenia (72%; 95% CI, 49%–90%), thrombocytopenia (40%; 95% CI, 18%–63%), anemia (39%; 95% CI, 17%–62%), leukopenia (28%; 95% CI, 5%–59%), and lymphopenia (15%; 95% CI, 0%–55%). Grade ≥ 3 CRS and ICANS were infrequent, with pooled prevalences of 2% (95% CI, 1%–3%) and 8% (95% CI, 6%–11%), respectively. Conclusion: This meta-analysis supports the role of liso-cel monotherapy in the treatment of R/R LBCL, demonstrating high ORR (78%) and CR (60%). The pooled efficacy estimates appeared higher than those reported in previous clinical trials. Liso-cel was also found to have a favorable safety profile. Grade 3 and 4 CRS and ICANS occurred rarely, at 2% and 8%, respectively. Mortality related to adverse events was also low, with a pooled incidence of 4%. However, clinicians should remain vigilant for severe hematologic toxicities, which occurred commonly. Limitations of this study include heterogeneity in study design, patient populations, and follow-up durations across included clinical trials and retrospective cohorts, which may affect generalizability. Nonetheless, this product-specific analysis provides valuable evidence to guide clinical decision-making for liso-cel monotherapy in R/R LBCL.