Safety Profile of Lisocabtagene Maraleucel in Relapsed or Refractory Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis of Clinical and Real-World Data
Introduction/Background/Significance: Chimeric antigen receptor (CAR) T-cell therapies have transformed the landscape of treatment for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). However, their use remains limited in part due to concerns about significant toxicities associated with CAR T-cell products. Unique adverse events (AEs) such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can result in life-threatening complications. Severe cytopenias are also commonly observed. Newer-generation CAR T-cell products seek to improve these safety concerns. Lisocabtagene maraleucel (liso-cel) is a second-generation autologous CD19-directed product that is FDA-approved for use in R/R LBCL. While clinical trials have reported favorable safety findings, a comprehensive review of severe toxicities across clinical trials and real-world settings remains lacking.
Materials and Methods/Case Presentation/Objective: We conducted a systematic review and meta-analysis of studies reporting safety outcomes of liso-cel monotherapy in R/R LBCL. PRISMA guidelines were followed and PubMed, Embase, and Cochrane databases were searched. 11 total studies were included (n = 1206 patients), comprising five clinical trials and six retrospective real-world studies. Meta-analyses were performed using the R meta package and random-effects model was applied. Heterogeneity was assessed using the I2 statistic.
The primary outcome of our meta-analysis was prevalence of grade ≥ 3 AEs, including CRS and ICANS. Secondary endpoints included overall mortality, mortality due to disease progression, and mortality due to AEs.
Results/Description/Main Outcome Measures: In total, 11 studies were pooled for analysis (n = 1206). Grade ≥ 3 CRS and ICANS were infrequent, with pooled prevalence of 2% (95% confidence interval [CI] 1%–3%) and 8% (95% CI 6%–11%), respectively. The most common grade ≥ 3 AEs were hematological toxicities, 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%). Data on grade ≥ 3 infections were limited and insufficient for pooled analysis. The pooled overall mortality was 38% (95% CI 30%–46%). The pooled prevalence of mortality due to disease progression was 28% (95% CI 18%–38%). Mortality due to AEs was uncommon, with pooled prevalence of 4% (95% CI 3%–6%).
Conclusions: This meta-analysis supports the favorable safety profile reported in initial clinical trials for liso-cel monotherapy in R/R LBCL. Grade 3 or 4 CRS and ICANS were uncommon, with pooled prevalence of 2% and 8%, respectively, and most severe adverse events were hematological toxicities. These findings reinforce the importance of close hematological monitoring and supportive care during treatment. Variability in study design, patient populations, and practice settings across included clinical trials and retrospective cohorts may limit generalizability of this study. Nevertheless, this safety analysis offers meaningful evidence and insight to guide clinical decision making for LBCL patients receiving liso-cel.
