Cancer Medicine | Study on Cytokine Release Syndrome Management with Talquetamab for Relapsed/Refractory Multiple Myeloma

This article systematically evaluates the cytokine release syndrome (CRS) characteristics and management strategies of talquetamab in patients with relapsed/refractory multiple myeloma (RRMM), providing crucial safety data and treatment recommendations for clinical practice. The findings validate the applicability of existing CRS management guidelines and inform dose adjustments during repeat administration.

 

Literature Overview
This article titled 'Characterization and Management of Cytokine Release Syndrome From the MonumenTAL-1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma' published in Cancer Medicine summarizes the clinical manifestations and management approaches for CRS, a common immune-related adverse event in T-cell redirecting therapies (TCRT). Using data from the MonumenTAL-1 clinical trial, the study analyzes CRS incidence, severity, onset timing, and treatment interventions while exploring potential immunobiomarkers to provide critical reference for clinical applications.

Background Knowledge
Cytokine release syndrome (CRS) is a frequent immune-related adverse reaction in T-cell redirecting therapies (TCRT), characterized by systemic inflammatory responses, fever, hypotension, and multi-organ dysfunction. Talquetamab, a bispecific antibody targeting GPRC5D and CD3, treats RRMM - a plasma cell malignancy predominantly affecting elderly patients where some develop resistance or relapse after standard therapies, necessitating novel interventions. Effective CRS management is vital for TCRT safety, and this study further characterizes talquetamab-associated CRS to optimize clinical management strategies.

 

 

Research Methods and Experiments
This study enrolled RRMM patients without prior TCRT exposure, administering talquetamab at 0.4 mg/kg weekly or 0.8 mg/kg biweekly following premedication with corticosteroids, antihistamines, and antipyretics. Some patients received stepwise dose-escalation regimens to mitigate CRS risk. CRS grading followed American Society for Transplantation and Cellular Therapy (ASTCT) criteria, with analyses focusing on onset timing, duration, severity, and treatment interventions.

Key Conclusions and Perspectives

• CRS incidence was 79.0% and 74.5% in the weekly and biweekly dosing cohorts respectively, predominantly grade 1-2 with only isolated grade 3 events and no grade 4-5 CRS.
• Most CRS events occurred during dose-escalation phases, with approximately one-third of patients experiencing multiple CRS episodes. Tocilizumab treatment for initial CRS reduced subsequent episodes.
• CRS typically onset within 24 hours and lasted approximately 15–20 hours without significant differences between dosing schedules.
• Patients previously exposed to TCRT showed similar CRS incidence to treatment-naïve patients, demonstrating talquetamab's safety in pretreated populations.
• CRS onset correlated with changes in IL-6, IL-2R, and IFNγ levels, though no definitive predictive biomarkers were identified.
• Reduced CRS incidence during repeated dose-escalation suggests gradual re-administration approaches could minimize risks.
• CRS management strategies, including tocilizumab use, showed no negative impact on therapeutic efficacy with comparable overall response rates (ORR) between CRS-affected and unaffected patients.

Research Significance and Prospects
This study provides comprehensive talquetamab-associated CRS data, confirming alignment between clinical management strategies and current guidelines. Future research should validate CRS biomarkers and explore prophylactic tocilizumab applications in larger RRMM cohorts. Findings will optimize talquetamab administration protocols, enhancing treatment safety and patient care experiences.

 

 

Conclusion
Talquetamab demonstrates CRS incidence and severity comparable to other T-cell redirecting therapies, with most cases being low-grade and manageable. CRS management protocols (including tocilizumab administration) maintain therapeutic efficacy, supporting early clinical intervention and personalized treatment approaches. These findings provide essential guidance for CRS monitoring and management in clinical practice, facilitating broader application of talquetamab for RRMM treatment.

 

Niels W C J van de Donk, Ajai Chari, Thomas Martin, Christoph Heuck, and Maria‐Victoria Mateos. Characterization and Management of Cytokine Release Syndrome From the MonumenTAL‐1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma. Cancer Medicine.