Introduction: Talquetamab (Talq) is a first-in-class bispecific T-cell engager antibody directed against G protein-coupled receptor class C group 5 member D (GPRC5D), approved to treat relapsed/refractory multiple myeloma (RRMM). In the MonumenTAL-1 study, an overall response rate was noted in 70% of patients with 23% achieving a complete response. Cytokine release syndrome (CRS) occurred during the step-up dosing phase at a rate of 77%; however, there was no breakdown by step-up dose (SUD). This study sought to characterize CRS rates after each Talq SUD in a real-world setting to discern whether patient hospitalization is required for the entire period of the step-up dosing schedule.
Methods: In this retrospective study, patients with RRMM who received Talq between September 2023 and May 2024 were identified via the institutional plasma disorders database; patients were selected if they completed the step-up dosing phase for the weekly or biweekly dosing schedule. Chart review was performed to collect patient demographics, disease features, prior lines of therapy (LOT), start dates of Talq SUDs, and CRS onset/grades. The Chi-square/Fisher exact test was used to compare CRS rates after each Talq SUD. Differences in time to onset of CRS between the SUDs were compared using the Kruskal Wallis test. Logistic regression analysis was performed to assess the impact of prior exposure to T-cell redirection therapy (TCRT) on CRS incidence. All statistical analyses were performed in SPSS (version 29).
Results: 36 patients completed the Talq step-up dosing phase; of whom 16 received the biweekly step-up dosing schedule. The median age was 65 years (range: 41-85 years), and 42% (n=15) were male. The median number of prior LOT was 7 (range: 4-16), and 69% (n=25) had prior TCRT. High risk cytogenetic features [t(4;14), t(14;16), t(14;20), TP53 mutations, del(17p) and 1q amplification] were present in 50% (n= 18) of patients. With an overall incidence of 77%, CRS occurred at a rate of 33% (n=12), 31% (n=11), 11% (n=4) and 6% (n=1) with SUD1, SUD2, SUD3 and first full dose (FFD, p=0.03), respectively. Pairwise comparisons revealed statistically significant differences in CRS rates between SUD1 and SUD3 (p=0.04), SUD1 and FFD (p=0.04) as well as SUD2 and FFD (p=0.04). Grade 2 CRS occurred in 6% of patients with SUD1, 14% with SUD2, 6% with SUD3 and 0% with FFD (p=0.40). Logistic regression analysis indicated no association between prior exposure to TCRT and CRS incidence (OR: 0.62, 95% CI: 0.13-2.60; p=0.61). The median time to onset of first CRS event was 20 hours (range: 11-40 hours), 13 hours (8-34 hours), 28 hours (24-31 hours) and 31 hours with SUDs 1, 2, 3 and FFD (p=0.33), respectively.
Conclusions: Our real-world data indicated that the Talq FFD was well tolerated, characterized by a significantly low incidence/severity of CRS events. Reducing length of hospital stay with the Talq step-up dosing schedule, and administration of Talq FFD in outpatient settings could be considered in clinical practice.