治疗前高疾病负荷是大 B 细胞淋巴瘤 CD19 CAR-T 细胞治疗后感染并发症的危险因素

Infection has emerged as the chief cause of non-relapse mortality (NRM) post CD19-targeting chimeric antigen receptor T-cell therapy (CAR-T) therapy. Even though up to 50% of patients may remain infection-free, many suffer multiple severe, life-threatening, or fatal infectious events. The primary aim of this study was to explore severe and life-threatening infections post licensed CAR-T therapy in large B-cell lymphoma, with a focus on the role of disease burden and disease sites in assessing individual risk.

We sought to understand the cohort of patients who experience 2 infections and those at the highest risk of infectious NRM.

Our analysis identifies a higher disease burden after bridging therapy as associated with infection events. Those developing 2 infections emerged as a uniquely high-risk cohort, particularly if the second (or beyond) infection occurred during an episode of immune effector cell-associated neurotoxicity syndrome (ICANS) or while on steroids and/or anakinra for ICANS.

Herein, we also describe the first reported cases of "CAR-T cold sepsis," a phenomenon characterized by the lack of an appreciable systemic inflammatory response at the time of detection of infection.

We propose a risk-based strategy to encourage heightened clinician awareness of cold sepsis, with a view to reducing NRM.