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

Purpose: 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.

Methods: 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.

Results: 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]).

Conclusion: 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.