Cancer Medicine | Study on the Management of Cytokine Release Syndrome in Talquetamab-Treated Patients With Relapsed/Refractory Multiple Myeloma

This study systematically assessed the cytokine release syndrome (CRS) profiles and management strategies of talquetamab in patients with relapsed/refractory multiple myeloma, providing critical safety data and therapeutic recommendations for clinical practice. The findings validate the applicability of CRS management guidelines and offer evidence-based dose adjustment protocols for repeat administration.

 

Literature Overview
This article '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, systematically reviews the clinical manifestations and management strategies of cytokine release syndrome (CRS) associated with T cell redirecting therapies (TCRT) in talquetamab treatment. The study analyzed CRS incidence, severity, onset timing, and treatment interventions using MonumenTAL-1 clinical trial data, while exploring related immunobiomarkers to provide clinical reference information.

Background Knowledge
Cytokine release syndrome (CRS) is a common immune-related adverse reaction in T cell redirecting therapy (TCRT), characterized by systemic inflammatory response, fever, hypotension, and multiple organ dysfunction. Talquetamab is a bispecific antibody targeting GPRC5D and CD3, specifically developed for treating relapsed/refractory multiple myeloma (RRMM). Multiple myeloma represents a plasma cell malignancy predominantly affecting elderly patients, with some individuals demonstrating resistance to existing therapies or disease recurrence requiring novel interventions. Effective CRS management is critical for TCRT treatment safety. This study further characterizes talquetamab-associated CRS to optimize clinical management strategies.

 

 

Research Methods and Experiments
The study enrolled treatment-naïve RRMM patients receiving weekly (0.4 mg/kg) or biweekly (0.8 mg/kg) talquetamab regimens. Prophylactic premedication included corticosteroids, antihistamines, and antipyretics before drug administration. Some patients underwent stepwise dose escalation to mitigate CRS risk. CRS grading followed the American Society for Transplantation and Cellular Therapy (ASTCT) criteria, with comprehensive analysis of onset timing, duration, severity, and treatment interventions.

Key Conclusions and Perspectives

• CRS incidence was 79.0% in the weekly talquetamab dosing group and 74.5% in the biweekly group, predominantly Grade 1-2 severity with only isolated Grade 3 events and no Grade 4-5 CRS cases.
• Most CRS events occurred during the dose-escalation phase, with approximately one-third of patients experiencing multiple CRS episodes. Tocilizumab intervention for initial CRS demonstrated reduced recurrence rates.
• CRS typically developed within 24 hours post-administration, with median duration of 15–20 hours showing no significant differences between dosing schedules.
• CRS incidence in patients with prior TCRT exposure remained comparable to treatment-naïve individuals, indicating talquetamab's safety profile in previously exposed 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 stepwise titration strategies for re-administration.
• CRS management did not compromise therapeutic efficacy, with similar overall response rates (ORR) observed between CRS-affected and non-CRS patients.

Research Significance and Prospects
The study provides systematic characterization of talquetamab-related CRS, validating the consistency between clinical management strategies and established guidelines. Future research requires larger cohorts to confirm CRS biomarkers and evaluate prophylactic tocilizumab applications in RRMM. These findings enable optimized clinical implementation of talquetamab, enhancing treatment safety and patient experience.

 

 

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

 

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.