I 期儿童 CAR-T 细胞试验前 30 天不良事件的全面分析

The tremendous success of chimeric antigen receptor (CAR) T cells in children and young adults (CAYAs) with relapsed/refractory B-cell acute lymphoblastic leukemia is tempered by toxicities such as cytokine release syndrome (CRS). Despite expansive information about CRS, profiling of specific end-organ toxicities secondary to CAR T-cell therapy in CAYAs is limited. This retrospective, single-center study sought to characterize end-organ specific adverse events (AEs) experienced by CAYAs during the first 30 days after CAR T-cell infusion. AEs graded using Common Terminology Criteria for Adverse Events were retrospectively analyzed for 134 patients enrolled in 1 of 3 phase 1 CAR T-cell trials (NCT01593696, NCT02315612, and NCT03448393), targeting CD19 and/or CD22. A total of 133 patients (99. 3%) experienced at least 1 grade 3 ( Gr3) AE across 17 organ systems, of which 75 (4.

4%) were considered dose- or treatment-limiting toxicities. Excluding cytopenias, 109 patients (81. 3%) experienced a median of 3 Gr3 noncytopenia (NC) AEs. The incidence of Gr3 NC AEs was associated with the development and severity of CRS as well as preinfusion disease burden ( 25% marrow blasts). Although those with complete remission trended toward experiencing more Gr3 NC AEs than nonresponders (median, 4 vs 3), nonresponders experiencing CRS (n = 17; 37.

8%) had the highest degree of NC AEs across all patients (median, 7 vs 4 in responders experiencing CRS). Greater understanding of these toxicities and the ability to predict which patients may experience more toxicities is critical as the array of CAR T-cell therapies expand. This retrospective study was registered at www. clinicaltrials. gov as NCT03827343.