Biomarkers for predicting CAR-T cell therapy outcomes in B-cell acute lymphoblastic leukemia: a systematic review

Resumo original em inglês

O que aconteceu

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), yet challenges such as cytokine release syndrome (CRS), neurotoxicity (ICANS), and variable long-term efficacy persist. This systematic review evaluates the role of biomarkers in predicting CAR-T therapy outcomes, toxicity risks, and guiding personalized treatment strategies.

Following PRISMA guidelines, we systematically searched PubMed, Web of Science, and Embase for studies published between 2018-2024. A total of 33 studies involving 2,095 patients were included in the analysis.

Despite promising insights, heterogeneity in toxicity grading systems, inconsistent biomarker thresholds, and retrospective study designs limit clinical standardization. Future directions emphasize cytoreductive bridging therapies, biomarker-guided combinatorial approaches (e.g., MDM2 inhibitors for TP53 mutations), and multicenter validation of integrated predictive models to optimize personalized CAR-T therapy strategies.

O que encontraram

Key findings identified tumor burden and minimal residual disease (MRD) as dual-predictive biomarkers. High tumor burden (≥40% blasts) correlated with reduced complete remission rates (87% vs. 100%) and increased CRS/ICANS risks, while MRD negativity (NGS threshold 5.2% in CD4+ cells) and peak expansion kinetics, linked efficacy to toxicity trade-offs. Genetic biomarkers (IKZF1 mutations, complex karyotypes) and biochemical indicators (m-EASIX >6.2, ferritin ≥10,000 ng/mL) further stratified risks. Unidirectional efficacy biomarkers included T-cell subsets (e.g., CD8+ naive T cells) and B-cell aplasia, while IL-6 dynamics specifically predicted CRS severity.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.