Low Dose Tocilizumab for Mitigation of Cytokine Release Syndrome With T-Cell Engaging Bispecific Antibodies

BACKGROUND: Cytokine release syndrome (CRS) is one of the most common adverse effects of T-cell engaging bispecific antibodies (T-BsAbs) during the step-up dosing (SUD) phase of treatment. Previous studies demonstrated that a single prophylactic tocilizumab (Toci) dose of 8 mg/kg mitigated the incidence CRS events. Herein, we evaluated the efficacy of a low Toci dose (Toci-lo) of 4 mg/kg for CRS prophylaxis during the SUD phase. METHODS: The study included relapsed/refractory multiple myeloma patients, treated with T-BsAbs and received prophylactic Toci-lo (cohort 1) administered prior to the first SUD only. A historical patient cohort that did not receive Toci prophylaxis was identified (cohort 2) for comparison. The CRS rates were compared between the 2 cohorts using the Fisher's exact/Chi-square test. Univariate/multivariate logistic regression analysis was performed to estimate the odds of CRS events with Toci-lo prophylaxis. RESULTS: A total of ninety patients were included in the final analysis (56 in cohort 1 and 34 in cohort 2). CRS rate was significantly lower in cohort 1 (21%, 95% CI:10.7%-37.8%) compared to cohort 2 (55%, 95% CI: 38.0%-70.8%; P = .009). Grade 2 CRS rates were 2% and 21% in cohorts 1 and 2, respectively (P = .0041). Based on multivariate logistic regression, Toci-low was associated with a significant reduction in CRS rates (OR: 0.2, 95% CI: 0.06-0.65; adjusted P = .01). CONCLUSION: Based on our findings, prophylactic Toci-lo proved to be effective in reducing CRS events during the SUD phase of treatment with T-BsAbs. The implementation of this prophylactic strategy in clinical practice might minimize healthcare expenditures.