P911: evaluation of prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (crs) to inform the management of patients (pts) treated with teclistamab in majestec-1

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Teclistamab is the first BCMA × CD3 bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma (RRMM). In MajesTEC-1, CRS occurred in 72.1% of pts treated at the recommended phase 2 dose (RP2D) of weekly teclistamab 1.5 mg/kg (50.3% grade [gr] 1; 21.2% gr 2; 0.6% gr 3), and was successfully managed using toci in 36.4% of pts (± other interventions) without affecting response to teclistamab. Emerging data show that prophylactic administration of toci prior to first dose of bispecific antibodies reduces CRS incidence and severity, which may facilitate outpatient initiation of therapy. Aims: The current analysis includes the first prospective study of effects of prophylactic toci on incidence and severity of CRS with teclistamab. Methods: Eligible pts were aged ≥18 y with RRMM and had previously received a PI, IMiD, and anti-CD38 antibody. All pts provided informed consent. Pts received subcutaneous teclistamab (following 2 step-up doses) in a prospective exploratory cohort at the RP2D or in a fixed-dose cohort. Toci (single 8 mg/kg IV dose) was given ≤4 hours before the first teclistamab step-up dose. CRS was graded per Lee et al 2014 and managed per institutional guidelines. Results: 14 pts were included: median age 64 y (range 50–82); all pts had ECOG score ≤1 and ISS I/II; 91% had standard cytogenetic risk; 21% had extramedullary plasmacytomas; 31% had ≥30% BMPCs; median 4 prior lines of therapy (range 2–7); 64% triple-class refractory. Median follow-up was 1.2 mo (range 0.2–4.6). CRS occurred in 4 pts (29%; no gr ≥3 CRS); 1 had a subsequent CRS event (table). Median time to onset was 2 d (range 1–3); median duration was 2 d (range 2–4); all events were managed with toci and resolved without teclistamab discontinuation. 7 of 14 pts had gr 3/4 neutropenia (consistent with the overall MajesTEC-1 population). 2/14 had a gr 3/4 infection. 2/14 had a neurotoxicity AE. Of the response evaluable patients, 4/7 responded. Cytokine and PK data in additional pts with longer follow-up will be presented to further inform pt management. Summary/Conclusion: A single dose of toci before teclistamab treatment appeared to reduce the incidence of CRS relative to the overall MajesTEC-1 study population with no new safety signals and no evidence of impact on response to teclistamab considering the short follow-up. Prophylactic toci has the potential to reduce CRS risk in pts with disease profiles suitable for outpatient dosing, reducing the burden of hospitalization during teclistamab step-up dosing. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.Keywords: B-cell maturation antigen, Multiple myeloma, Cytokine release syndrome, Bispecific