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 (TCE) 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 chimeric antigen receptor (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. SIGNIFICANCE: Scores such as HTX, EASIX, and m-EASIX have emerged as helpful tools to enable risk stratification before CAR T-cell therapy. In this study, we demonstrate their utility in patients with RRMM receiving TCEs. HTX ≥3 and m-EASIX > median (>0.86) proved to be risk markers for infections, therapeutic interventions, and poor outcomes. See related commentary by Banerjee and Dhodapkar, p. 345.