Infections following combined therapy with a GPRC5DxCD3 bispecific antibody, talquetamab, and an interleukin-6 receptor inhibitor, tocilizumab, in multiple myeloma patients

Abstract Background The treatment landscape for multiple myeloma has been significantly advanced by the FDA-approval of talquetamab, a GPRC5DxCD3 bispecific antibody. While effective in depleting plasma cells, and to some extent T-cells, talquetamab therapy is associated with an increased risk of infections. A notable gap in current research is the limited information regarding infection rates in multiple myeloma patients treated with talquetamab who also received an Interleukin-6 receptor inhibitor such as tocilizumab. Tocilizumab is used for the prophylaxis and treatment of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Given the complex relationship between talquetamab's immunomodulatory effects and the use of tocilizumab, this study aims to assess infection rates in this specific patient population using real-world data (RWD). Methods A retrospective analysis of RWD from 83 healthcare organizations was carried out using the TriNetX database on Jul 23, 2025. We identified patients with multiple myeloma treated with talquetamab and stratified them into two cohorts: those who received a concomitant interleukin-6 receptor inhibitor tocilizumab, and those who did not. To minimize confounding factors, we employed a 1:1 propensity score matching for baseline age and prior immunoglobulin use. The index date was defined as the first administration of talquetamab. The primary outcomes were the incidence of infections including sepsis, respiratory, cytomegalovirus, and other specified infections all-cause mortality. Statistical analyses included the calculation of risk ratios (RR), odds ratios (OR), and hazard ratios (HR) with 95% confidence intervals (CI). Kaplan-Meier analysis with a log-rank test was used to compare survival probabilities. Results The study initially identified a total of 600 patients, with 280 patients receiving tocilizumab and 320 patients who did not. After propensity score matching, 290 patients were analyzed in each cohort. Our analysis revealed significant differences in outcomes between the two groups. Patients receiving talquetamab without tocilizumab demonstrated a substantially lower risk of all-cause mortality compared to those who received both treatments (20.7% vs. 31.0%; HR 0.709, 95% CI 0.503–0.999; p=0.038). The incidence of infections was markedly higher in the cohort receiving tocilizumab. Specifically, the patients who did not receive concomitant tocilizumab exhibited a lower risk of respiratory infections (27.6% vs. 37.9%; p=0.008) and other specified infections (41.4% vs. 58.6%; p<0.001). Interestingly, no statistically significant differences were observed between the two groups regarding the risk of sepsis (p=0.290) or cytomegalovirus infection (p=0.061). Conclusions RWD has demonstrated that multiple myeloma patients treated with the GPRC5DxCD3 bispecific antibody, talquetamab, in combination with the IL-6 receptor inhibitor, tocilizumab, exhibit an elevated risk for respiratory and other types of infections, as well as increased all-cause mortality. The administration of tocilizumab is crucial for the management of CRS and ICANS, necessitating a comprehensive understanding of infection risk factors to implement effective prevention and management strategies. Additional research is required to conduct a comparative analysis of patients treated with tocilizumab following CRS/ICANS associated with BCMA bispecific antibody therapy (teclistamab, elranatamab) and GPRC5D bispecific antibody therapy (talquetamab) considering that the type of bispecific antibody may serve as a confounding factor.