Cancer Medicine | Study on Cytokine Release Syndrome Management with Talquetamab in 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, providing critical safety data and treatment recommendations for clinical practice. The findings validate the applicability of existing CRS management guidelines and offer evidence for dose adjustments during repeat administrations.

 

Literature Overview
The 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, reviews the manifestations and management approaches of CRS—a common adverse reaction in T cell redirecting therapies (TCRT)—specifically in talquetamab treatment. Based on data from the MonumenTAL-1 clinical trial, the study analyzes CRS incidence, severity, onset timing, and treatment interventions while exploring the role of associated immunobiomarkers to provide critical reference information for clinical applications.

Background Knowledge
Cytokine release syndrome (CRS) is a frequent immune-related adverse event in T cell redirecting therapy (TCRT), characterized by systemic inflammatory responses, fever, hypotension, and multi-organ dysfunction. Talquetamab is a bispecific antibody targeting GPRC5D and CD3, indicated for treating relapsed/refractory multiple myeloma (RRMM). Multiple myeloma is a plasma cell malignancy predominantly affecting elderly patients, with some cases exhibiting resistance to existing therapies or disease relapse, necessitating novel treatment approaches. Effective CRS management is crucial for ensuring the safety of TCRT treatments. This study further characterizes talquetamab-associated CRS features and provides clinical management guidance.

 

 

Research Methods and Experiments
The study enrolled RRMM patients without prior TCRT exposure, who received talquetamab at either weekly 0.4 mg/kg or biweekly 0.8 mg/kg dosing regimens. Premedication with corticosteroids, antihistamines, and antipyretics was administered before drug infusion. Some patients underwent stepwise dose-escalation to mitigate CRS risk. CRS grading followed the American Society for Transplantation and Cellular Therapy (ASTCT) criteria, with analyses focused on onset timing, duration, severity, and treatment interventions.

Key Conclusions and Perspectives

• CRS incidence rates were 79.0% and 74.5% in weekly and biweekly dosing groups respectively, predominantly grade 1-2 events with only isolated grade 3 cases and no grade 4-5 CRS observed.
• 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 recurrence rates.
• CRS onset typically occurred within 24 hours, with durations averaging 15–20 hours showing no significant differences between groups.
• CRS incidence in patients with prior TCRT exposure was comparable to treatment-naïve patients, indicating talquetamab's safety in previously exposed populations.
• CRS onset was associated with changes in cytokine levels including IL-6, IL-2R, and IFNγ, though no definitive predictive biomarkers were identified.
• Reduced CRS incidence during repeat dose escalations suggests stepwise dose-increase strategies should be considered for re-administration.
• CRS management did not compromise therapeutic efficacy, with comparable overall response rates (ORR) between CRS-affected and non-CRS patients.

Research Significance and Prospects
This study provides comprehensive data on talquetamab-related CRS, demonstrating alignment between clinical management strategies and current guidelines. Future research should validate CRS biomarkers and preventive tocilizumab applications in larger RRMM cohorts. The findings contribute to optimizing talquetamab's clinical implementation and enhancing treatment safety and patient experience.

 

 

Conclusion
Talquetamab demonstrates comparable CRS incidence and severity profiles to other T cell redirecting therapies in RRMM patients, with most events being low-grade and manageable. CRS management strategies (e.g., tocilizumab use) do not compromise therapeutic efficacy, supporting early clinical intervention and personalized treatment approaches. The findings provide critical evidence for clinical monitoring and management of CRS while endorsing talquetamab's broad application in 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.