Cancer Medicine | Study on Cytokine Release Syndrome Management of Talquetamab in Treating 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 support the applicability of existing CRS management guidelines and offer evidence for dose adjustments during repeated administrations.

 

Literature Overview
The 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, reviews the manifestations and management approaches of CRS, a common adverse reaction in T-cell redirecting therapies (TCRT), during talquetamab treatment. Based on MonumenTAL-1 clinical trial data, this study analyzes CRS incidence, severity, onset timing, treatment interventions, and explores related immunobiomarkers, offering valuable clinical reference.

Background Knowledge
Cytokine release syndrome (CRS) is a frequent immune-related adverse reaction in T-cell redirecting therapies (TCRT), characterized by systemic inflammatory response, fever, hypotension, and multi-organ dysfunction. Talquetamab is a bispecific antibody targeting GPRC5D and CD3, designed for treating relapsed/refractory multiple myeloma (RRMM). Multiple myeloma is a plasma cell malignancy predominantly affecting elderly patients, with some individuals developing resistance to existing therapies or experiencing relapse, necessitating novel treatment approaches. Effective CRS management is critical for ensuring TCRT treatment safety. This study further characterizes talquetamab-related CRS features and provides clinical management strategy support.

 

 

Research Methods and Experiments
The study enrolled TCRT-naïve RRMM patients receiving weekly (0.4 mg/kg) or biweekly (0.8 mg/kg) talquetamab treatment. Pre-medications including corticosteroids, antihistamines, and antipyretics were administered before drug infusion. Some patients underwent stepwise dose-escalation regimens to mitigate CRS risk. CRS grading followed the 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% in the weekly dosing group and 74.5% in the biweekly group, predominantly grade 1-2 with only isolated grade 3 events and no grade 4-5 CRS.
• Most CRS events occurred during the dose-escalation phase, with approximately one-third of patients experiencing multiple CRS episodes. Tocilizumab treatment for initial CRS reduced subsequent recurrence rates.
• CRS typically onset within 24 hours and lasted 15-20 hours on average, with no significant differences between dosing schedules.
• CRS incidence in patients previously exposed to TCRT was comparable to treatment-naïve patients, suggesting talquetamab can be safely administered to pre-exposed individuals.
• CRS onset correlated with fluctuations in cytokine levels (IL-6, IL-2R, IFNγ), though no definitive predictive biomarkers were identified.
• Repeated dose escalations demonstrated lower CRS incidence, suggesting stepwise dose-escalation strategies should be considered 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
This study provides comprehensive talquetamab-associated CRS data, confirming alignment between clinical management strategies and current guidelines. Future research requires larger cohorts to validate CRS biomarkers and assess prophylactic tocilizumab efficacy in RRMM. These findings will optimize talquetamab clinical application while enhancing treatment safety and patient experience.

 

 

Conclusion
Talquetamab demonstrates comparable CRS incidence and severity to other T-cell redirecting therapies in RRMM patients, with most cases being low-grade and manageable. CRS management strategies (e.g., tocilizumab use) do not impair therapeutic efficacy, supporting early clinical intervention and individualized treatment approaches. The study provides critical evidence for CRS monitoring and management, facilitating broader adoption of talquetamab in RRMM clinical practice.

 

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.