Phase 2 emapalumab IFN-γ–neutralizing antibody to prevent BsAb CRS/ICANS in R/R MM, LBCL

This Phase 2, single-arm prophylaxis study tests whether emapalumab (Gamifant)—an interferon-gamma (IFN-γ)–blocking monoclonal antibody—can reduce cytokine release syndrome (CRS) and/or immune effector cell–associated neurotoxicity syndrome (ICANS) in patients receiving outpatient bispecific T-cell engager (TCE) antibodies. Participants receive prophylactic emapalumab before their intended “standard” bispecific antibody therapy for relapsed/refractory multiple myeloma (2nd line+) or relapsed/refractory large B-cell lymphoma (2nd line), with endpoints spanning feasibility, safety (including infection risk relevant to IFN-γ neutralization), and toxicity prevention efficacy. The trial is sponsored by NYU Langone Health; the preventive strategy is scientifically interesting because it targets an upstream inflammatory driver (IFN-γ) rather than the more common reactive approach once CRS emerges. Today, many BsAbs are delivered with step-up dosing and close monitoring, and CRS is typically managed with supportive care and IL-6 blockade (e.g., tocilizumab), while ICANS management often relies on neurologic monitoring and steroids—this study asks whether pre-emptive cytokine neutralization can make outpatient BsAb delivery safer without blunting anti-tumor activity.