Efficacy and Safety of Prophylactic Tocilizumab in Patients with Multiple Myeloma Receiving Bispecific Antibodies: A Systematic Review and Meta-Analysis

Background: Cytokine release syndrome (CRS) remains a major toxicity associated with bispecific antibody (BsAb) therapy in relapsed/refractory multiple myeloma (RRMM). Prophylactic IL-6 receptor blockade with tocilizumab has emerged as a potential strategy to mitigate CRS; however, its efficacy and safety have not been systematically evaluated. Methods: Databases were searched for studies evaluating prophylactic tocilizumab in patients with RRMM receiving BsAb therapy. Comparative and single-arm studies were included. The primary outcome was CRS incidence. Secondary outcomes included CRS severity, adverse events, hospitalization, and antimyeloma efficacy. Pooled risk ratios (RRs) were calculated using random-effects models due to heterogeneity across studies. Results: Eight studies encompassing 704 patients were included, comprising five cohorts and three single-arm trials. Meta-analysis of three comparative studies demonstrated that prophylactic tocilizumab is associated with lower all-grade CRS incidence (RR 0.29, 95% CI 0.16–0.53; p < 0.0001), with moderate heterogeneity (I² = 59%). A pooled analysis of two studies evaluating grade ≥2 CRS showed a numerically lower risk with prophylaxis, although this did not reach statistical significance (RR 0.22, 95% CI 0.02–2.57; p = 0.23). CRS events were predominantly low grade, short-lived, and occurred during step-up dosing. ICANS was uncommon, and infection and hematologic toxicity rates were comparable between groups. No signal of reduced overall response rate was observed (RR 1.21, 95% CI 0.91–1.62; p = 0.19). Conclusion: Prophylactic tocilizumab is associated with lower CRS incidence without compromising efficacy in RRMM patients receiving BsAb therapy. Prospective randomized studies are warranted to confirm these findings and refine prophylactic strategies.