Predicting CRS in bsAb therapy – the Epworth experience

Abstract

Bispecific antibodies (bsAbs) represent a major advancement in the treatment of hematologic malignancies. However, their use is frequently complicated by cytokine release syndrome (CRS)—a common and potentially life-threatening immune-mediated toxicity that typically arises early in treatment.. Severe CRS can result in multi-organ dysfunction and delayed hematopoietic recovery, highlighting the importance of early risk identification to guide preemptive management, reduce hospitalization time, and ensure treatment continuity. Disease burden has emerged as one of the strongest predictors of severe CRS following bispecific T cell-engager therapy. Several cytokines, including sgp130, IL-6, and IFN-γ, have been proposed as predictive markers in recent CAR-T cell models. Composite scoring systems such as the Endothelial Activation and Stress Index (EASIX)—calculated as (creatinine × LDH)/platelets—and its derivatives (EASIX-F, EASIX-FC) have shown promise in stratifying CRS risk . Ferritin, a widely accessible acute-phase reactant, has gained interest for its potential prognostic role in CAR-T-related CRS yet its predictive value in the context of bsAb therapy is yet to be evaluated.