Defining the Rates of Cytokine Release Syndrome Associated With Talquetamab Step-up Doses

Talquetamab is a G protein-coupled receptor class C group 5 member D T-cell-engaging antibody, approved for relapsed/refractory multiple myeloma (RRMM). In the MonumenTAL-1 clinical trial, cytokine release syndrome (CRS) occurred at a frequency of 77%; however, there was no assessment of CRS rates by step-up dose. The primary objective of this study was to characterize CRS rates after each talquetamab step-up dose in a real-world setting.

Patients with RRMM who completed the talquetamab once a week or once every 2 weeks step-up dosing schedule between September 2023 and November 2024 were identified via the institutional database. CRS rate after each talquetamab step-up dose was compared using the chi-square/Fisher's exact test. The Kruskal-Wallis test was used to compare difference in median time to the CRS onset. Multivariate logistic regression analysis was performed to identify predictors of CRS.

Fifty patients completed the talquetamab step-up dosing phase during the study period; CRS occurred at a rate of 80%. Pairwise comparisons revealed significant differences in CRS rates between the fourth dose (4%) and each of step-up dose 1 (28%, P = .014) and 2 (34%, P = .003). The only CRS event with fourth dose was grade 1. The median time to onset of first CRS did not differ significantly between step-up doses (P = .441). Previous exposure to T-cell-redirecting therapy had no impact on CRS incidence (odds ratio: 0.20 [95% CI, 0.03 to 1.10]).

Our findings suggested that the fourth talquetamab dose could be administered in outpatient settings given its high tolerability. The reduced hospitalization period for talquetamab step-up dosing could reduce health care expenses.