Risk factors for CRS and ICANS with Bispecific Antibodies for Aggressive Lymphomas

Bispecific antibodies (BsAbs) are effective treatments in aggressive B‑cell lymphomas but carry immune-mediated risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), particularly during the first cycle. We analyzed 255 patients receiving BsAbs across 14 institutions to identify predictors of CRS/ICANS. CRS occurred in 31% (Grade 3+: 5%) and ICANS in 8% (Grade 3+: 2%) of patients, with no significant differences across glofitamab, mosunetuzumab, or epcoritamab. CRS rates with glofitamab and epcoritamab as monotherapy were lower than reported in trials. In multivariable analysis, concurrent systemic chemotherapy was associated with Grade 2+ CRS, and the development of any-grade CRS and elevated ferritin independently was associated with ICANS. All patients with Grade 3+ CRS had very high serum C-Reactive Protein (sCRP, ≥15 mg/L) and elevated ferritin (>336 ng/mL) when available. These findings identify candidate laboratory thresholds and treatment related factors that warrant prospection validation for risk stratification and outpatient BsAb administration.