Evaluation of the Diagnostic Performance of Plasma Metagenomic Next-Generation Sequencing in Febrile Events in the First 30 Days after Chimeric Antigen Receptor T Cell Infusion

Abstract

Chimeric antigen receptor-modified T cell (CAR-T) therapy is a promising novel immunotherapy for hematologic malignancies, and the diagnosis of infection after CAR-T infusion (CTI) presents challenges for clinicians. Plasma metagenomic next-generation sequencing (mNGS) has been shown to be a reliable diagnostic approach for infection, especially in immunocompromised patients. We aimed to investigate the diagnostic performance of plasma mNGS for infection in the first 30 days after CTI. A cohort of 153 patients who experienced a total of 170 febrile events during the first 30 days post-CTI were enrolled. Of these events, 51 were evaluated with both mNGS and CDM and 119 were assessed by conventional detection methods (CDM) only. We also explored the epidemiology of infections and differences in infection complications in cases with severe (>2) and moderate (≤2) cytokine release syndrome (CRS). Cases with febrile events were clinically divided into an infection group (IG) (95 of 170; 55.9%) and a noninfection group (NIG) (75 of 170; 44.1%). The sensitivity and specificity of mNGS for the diagnosis of infectious complications in the first 30 days after CTI were 69.2% and 89.2%, respectively, with the sensitivity superior to that of culture (P < .001). More infection cases assessed with both mNGS and CDM than those assessed with CDM only were laboratory-confirmed (63.9% versus 11.9%; P < .001). The serum C-reactive protein level was higher and the IFN-γ level was lower in the IG group, particularly in cases with CRS grade ≤2. Infection is a common complication in the first 30 days after CTI. The addition of mNGS to CDM improved the diagnostic yield, and mNGS showed relatively high sensitivity and specificity in post-CAR-T therapy febrile events.