7517 Background: Emerging data suggest that administering toci prior to bispecific antibodies reduces the incidence of CRS, which may support outpatient therapy initiation. We previously showed that the incidence of CRS with teclistamab, the first approved BCMA×CD3 bispecific antibody with weight-based dosing for the treatment of pts with triple-class exposed RRMM, was reduced from 72% in the overall MajesTEC-1 study population to 26% in a cohort receiving a single dose of toci before the first teclistamab step-up dose. Here, we present an updated analysis with longer-term follow-up. Methods: Pts with triple-class exposed RRMM received subcutaneous teclistamab 1.5 mg/kg weekly in a prospective exploratory cohort or at a comparable fixed dose, following 2 step-up doses. Toci 8 mg/kg was given intravenously ≤4 hours before the first teclistamab step-up dose. CRS was graded per Lee et al ( Blood 2014;124:188-95) and managed per the study protocol. Results: This analysis included 24 pts with median follow-up 8.1 months (range, 0.9–13.2). Median age was 72 years (range, 50–82); 100% had ECOG PS score ≤1; 96% had International Staging System stage I/II; 74% had standard-risk cytogenetics; 21% had extramedullary plasmacytomas; 33% had ≥30% bone marrow plasma cells (biopsy or aspirate). Pts had a median of 4 prior lines of therapy (range, 2–9); 58% were triple-class refractory. CRS occurred in 6 pts (25%; 2 grade 1, 4 grade 2, no grade ≥3); 3 pts each had 1 recurrent CRS event. Median time to CRS onset was 2 days (range, 1–3); median duration was 2 days (range, 2–4). CRS was managed with additional toci in 5/6 pts and steroids in 1/6; all CRS events resolved and none led to teclistamab discontinuation. Most common adverse events (AEs; any grade/grade 3/4) were infections (79%/25%), neutropenia (63%/63%), and anemia (58%/25%); 5 pts had a neurotoxicity AE (grade 1 dizziness; grade 1 headache; grade 1 insomnia; grade 2 headache; grade 2 immune effector cell-associated neurotoxicity syndrome). Overall response rate (n=22) was 73% (59% very good partial response or better). Timing of interleukin (IL)-6 induction in the prophylactic toci cohort was consistent with the phase 1 MajesTEC-1 population, with higher IL-6 levels as observed in other studies of IL-6 receptor-blocking antibodies. Conclusions: Prophylactic toci reduced the incidence of CRS with teclistamab, with a 65% relative reduction vs the overall MajesTEC-1 population (grade 1, 8% vs 50%; grade 2, 17% vs 21%). No new safety signals or impact on response to teclistamab was observed with longer follow-up. Prophylactic toci may be a useful measure to consider when selecting pts for outpatient administration of teclistamab in the future. This approach is being evaluated in the phase 2, multicenter, prospective OPTec study (NCT05972135). Clinical trial information: NCT03145181 / NCT04557098 .