•Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are potentially fatal toxicities of bispecific antibody (BsAb) therapy.

•Elranatamab is a BCMA-directed BsAb requiring step-up dosing, the period of highest CRS risk.

•Prophylactic tocilizumab, an IL-6 receptor antagonist, may mitigate these toxicities and enable outpatient step-up dosing.

•Strategies that reduce CRS and ICANS may lower morbidity and mortality.

•Primary outcomes: Rates of CRS and ICANS

•Secondary outcomes: Overall survival, infection, treatment delay, and treatment discontinuation

•Retrospective cohort of 86 patients receiving elranatamab step-up dosing at Moffitt Cancer Center, Oct 2023 – Mar 2026.

•Patients treated in both inpatient and outpatient settings.

•42 (49%) received prophylactic tocilizumab prior to step-up dosing.

•CRS and ICANS graded by ASTCT consensus criteria.

•Fisher exact tests, Kaplan–Meier with log-rank, and Cox regression (R 4.5.0).

•Absolute rates of CRS (22% vs 30%) and ICANS (12% vs 14%) were lower with prophylactic tocilizumab, but not significantly so.

•Tocilizumab was associated with significantly less treatment discontinuation in prior-BCMA, prior CAR-T, and age >65 subgroups.

•Discontinuation and treatment delay were the strongest predictors of death.

•No ICANS occurred in the 16 outpatients, all of whom received prophylaxis.

•Prospective study is warranted, particularly for outpatient dosing.