Safety and efficacy of allogeneic CAR-T cells in B-cell malignancies: A systematic review and meta-analysis.

Abstract

e19530 Background: Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proven effective in recent trials for patients with B cell malignancies, who relapsed after stem cell transplantation. Genetically modified allogeneic CAR T-cells used in advanced B cell malignancy engage with multiple target allo-antigens along with CD19 and/or CD20, leading to elimination of malignant B cells resulting in a potent graft versus malignancy effect with avoidance of tumor escape. Some concerns regarding their use exist like life-threatening graft-versus-host disease (GVHD) and rapid clearance by the host immune system. This study summarises the efficacy and safety of allogeneic CAR-T therapy in B cell malignancies. Methods: A systematic literature search was conducted on PubMed, Embase, Cochrane and Clinicaltrials.gov from inception to Jan 26, 2022, using MeSH terms and keywords for B cell malignancies and CAR-T therapy. We also screened the data presented in various conferences and handpicked references from previous systematic reviews. Outcomes of interest were complete remission (CR), 1-year overall survival (OS), GVHD, cytokine release syndrome (CRS), and immune effector cell associated neurotoxicity (ICANS). Proportional outcomes were pooled using a random effects model (Freeman-Tukey double arcsine transformation) in OpenMetaAnalyst software. Results: The initial search retrieved 1247 articles. After excluding reviews, duplicates and non-relevant articles, we included data from 9 clinical trials (n = 146 patients). The most common malignancy was acute lymphoblastic leukemia (125 patients, 86%). The median age of patients ranged from 19 to 49 years. All patients received CD19 targeting therapy and the cell dose administered ranged from 0.4×10^6 to 5×10^8 cells/kg. CR was reported in 93 of 146 patients, with a pooled rate of 63% (95% CI 47.4 - 78.6%; I2 78.5%). The pooled 1-year OS was 57.3% (95% CI 30.8 - 82%; I2 79.2%). The pooled proportion of GVHD was 9.4% (95% CI 3.1- 15.6%; I2 47.6%). The pooled CRS and ICANS rates were 59.3% (95% CI 30.5 - 88.1%; I2 95.2%) and 15.4% (95% CI 4.6 - 26.3%; I2 72.7%), respectively. Conclusions: Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in < 10% of patients. Although allogeneic CAR-T cells are showing promise, several trials are ongoing and we need longer follow up.[Table: see text]

Charting new paradigms for CAR-T cell therapy beyond current Achilles heels

“…Longer-term follow-up data from these trials will provide valuable insights into the durability of responses and the potential for adverse events. Continued research efforts are necessary to optimize allogeneic CAR-T cell therapies and address any challenges that may arise, ultimately advancing their clinical utility in treating various malignancies ( 106 ).…”