Clinical scores to predict toxicities and outcomes in patients with multiple myeloma undergoing bispecific T-cell engager therapy

The significant clinical benefit of bispecific T-cell engagers (TCEs) for the treatment of relapsed/refractory multiple myeloma (RRMM) may be offset by serious toxicities and treatment failure. Risk scores such as the CAR-HEMATOTOX (HTX), Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) can identify patients at risk for complications before CAR T-cell therapy, but their utility prior to TCE therapy remains elusive. We analyzed associations with outcomes and toxicities in independent discovery (n=123) and validation (n=155) cohorts treated with TCEs. Patients with HTX ≥ 3 or m-EASIX > median (> 0.86) had a significantly increased risk of prolonged hospitalization, antibiotic treatment and fever during step-up dosing. We also observed associations with cytopenias requiring therapeutic intervention, higher severe infection and intervention densities, as well as inferior response rates and reduced progression-free and overall survival. Our findings highlight the potential of these clinical scores to improve risk stratification before TCE therapy.