Adverse outcomes of CAR-T such as hematotoxicity with prolonged
cytopenia and infectious complications represent a challenging clinical problem after CAR-T therapy; however, current predictive models rely on blood counts and general inflammatory lab markers (
ferritin, CRP) only and lack mechanistic / functional insights. Prolonged cytopenias after CAR-T are associated with endothelial alteration, characterized by reduced ANG1, E-
selectin and MMP-1, and increased ANG2:ANG1 ratio, VCAM-1 and
Thrombomodulin early after CAR-T. It was found that Patients with high baseline sIL-2R and VCAM-1 not only show more prolonged
neutropenia and a more aplastic neutrophil
recovery but also experience more severe infectious complications. High baseline VCAM-1 is associated with significantly worse peak CD8 CAR-
T cell expansion and separates MM patients with worse overall response (Figure 5, Figure s5) Baseline sIL-2R and VCAM-1 have high
predictive value for
adverse outcomes, such as prolonged
neutropenia, severe infections and death, and can further improve existing models.