A systematic review and meta-analysis of shRNA–IL-6-engineered CAR-T cells for B-cell acute lymphoblastic leukemia: a stepping stone toward risk-free immunotherapy
Abstract
Abstract Clinical application of chimeric antigen receptor (CAR)-T cells, especially those targeting CD19, stands as a breakthrough in treating relapsed or refractory B-cell acute lymphoblastic leukemia. Yet, preventing immune-related adverse events, like severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remains a significant concern. This meta-analysis looked at the efficacy and safety of interleukin-6 knockdown CAR-T therapy. The study’s primary outcomes included the incidence of CRS, ICANS, and the number of patients achieving an early complete response (CR) and overall response (OR) rates at one-month post-infusion of anti-CD19 shRNA-engineered CAR-T cells. The random-effects model was used to estimate summary effects. Certainty of evidence was assessed using GRADE. Out of 275 studies screened, 7 studies were eligible (n = 178 patients). The pooled OR and CR rates were 88% (95% CI: 81–92) and 84% (95% CI: 78–89), respectively, with no heterogeneity detected. Among 147 patients, 116 (78%, 95% CI: 68–85) developed CRS, whereas 46 (28%, CI: 21%–35%) out of 178 were affected by severe grades (≥3). While ICANS was detected in 13 out of 159 patients (13%, CI: 2%–51%, I2 = 69.5%), three studies confirmed the absence of severe grade ICANS. According to GRADE assessment, current analysis presents low certainty of evidence supporting investigated outcomes, except for ICANS (any grade) that was deemed very low. More…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 178 participants or records.
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