Characterization and Management of Cytokine Release Syndrome From the MonumenTAL‐1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma

ABSTRACT Introduction Cytokine release syndrome (CRS) is a common adverse event associated with T‐cell redirection therapies (TCRT), including talquetamab, the first GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). We describe CRS with talquetamab and implications for clinical practice. Methods Patients without prior TCRT received talquetamab 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W), with two or three step‐up doses, respectively, plus pretreatment with a glucocorticoid, antihistamine, and antipyretic. A separate cohort of patients with prior TCRT received talquetamab at either the QW or Q2W schedule. CRS was graded per American Society for Transplantation and Cellular Therapy criteria and managed per study protocol. Results Across talquetamab QW ( n = 143), Q2W ( n = 145), and prior TCRT ( n = 51) cohorts, most CRS events occurred during step‐up doses and were grade 1 or 2; grade 3 CRS events were rare. Approximately one‐third of patients experienced more than one CRS event. Fewer patients experienced subsequent CRS events if tocilizumab was used versus not used to treat their first CRS event. Overall response rates with talquetamab were similar among patients with and without tocilizumab to manage CRS. Baseline characteristics were not associated with CRS incidence, recurrence, duration, or severity, whereas immune biomarkers showed some trends in association with CRS parameters. Conclusion CRS outcomes with talquetamab were consistent with those seen with other TCRT in RRMM, including teclistamab (BCMA×CD3 bispecific antibody), indicating a similar clinical approach, including early vigilance and prompt treatment of CRS. Trial Registration NCT03399799/NCT04634552