Prophylactic acetaminophen regimen to prevent cytokine release syndrome with teclistamab or talquetamab: A single-center experience.

Abstract

e19509 Background: Teclistamab-cqyv and talquetamab-tgvs are bispecific T-cell engagers approved for relapsed/refractory multiple myeloma (MM) after at least four lines of therapy. They redirect T-cells to target tumor cells by simultaneously binding to CD3 on T-cells and specific antigens on plasma cells (BCMA for teclistamab, GPRC5D for talquetamab). Cytokine release syndrome (CRS), a common adverse effect associated with more severe outcomes, developed in 72.1% of patients in MajesTEC-1 (50.3% grade 1; 21.2% grade 2) and 76% of patients in MonumenTAL-1 (57% grade 1; 17% grade 2). Neurotoxic adverse effects (ICANS) were also reported in 57% and 55% of patients, respectively. CRS is typically managed with acetaminophen and supportive care for mild to moderate cases versus tocilizumab and corticosteroids for more severe cases. However, in a 2023 single-center study, only 26.3% (n=38) of patients who received prophylactic tocilizumab developed CRS (21.1% grade 1; 2.6% grade 2). We hypothesized that prophylactic acetaminophen could also reduce CRS incidence cost-effectively without masking the onset of severe CRS. We report our single-center experience using 650 mg of acetaminophen every 6 hours to reduce CRS severity. Methods: Retrospective chart review was conducted for 17 patients who received teclistamab or talquetamab for refractory MM at our center between August 2023 and October 2024. We reported descriptive statistics and compared the incidence of CRS and ICANS in those who received prophylactic acetaminophen with teclistamab to available data from MajesTEC-1 and the prophylactic tocilizumab study. Results: All patients had progressive disease at time of therapy. Of the 15 patients who received prophylactic acetaminophen, 33.3% (5) developed CRS, all grade 1. CRS incidence for teclistamab with acetaminophen prophylaxis (n=12) was lower (33.3%) compared to MajesTEC-1 (72.1%) but slightly higher compared to prophylactic tocilizumab (26.3%). No patients developed ICANS. All were discharged after the planned 7 days of therapy with no infections. Conclusions: Our study suggests that in patients treated with teclistamab for refractory MM, prophylactic scheduled acetaminophen may reduce CRS incidence and severity compared to teclistamab alone. This regimen may provide a cost-effective alternative to tocilizumab with a lower risk of infections. Limitations include small sample size, comparison to historical data, and single-center, retrospective design, which affects generalizability. Prospective, multi-center studies are recommended to confirm efficacy.