Is headache a symptom of Cytokine Release Syndrome (CRS) in patients receiving talquetamab?

Headache as a Symptom of Cytokine Release Syndrome in Patients Receiving Talquetamab

Yes, headache is a recognized symptom of Cytokine Release Syndrome (CRS) in patients receiving talquetamab. 1

Understanding CRS in Talquetamab Therapy

• CRS is a disorder caused by the release of cytokines from bystander immune and non-immune cells following immunotherapy, including bispecific antibodies like talquetamab 1
• The onset of CRS is variable and dependent on the specific therapy and patient population, with peaks typically occurring 2-7 days after infusion, though delays of up to 3 weeks have been reported 1
• CRS is defined by the Common Terminology Criteria for Adverse Events (CTCAE) as a "disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia caused by the release of cytokines" 1

Clinical Presentation of CRS with Talquetamab

• Presenting symptoms of CRS in patients receiving talquetamab include fever (which is required at onset for diagnosis), tachycardia, hypoxia, nausea, headache, rash, shortness of breath, hypotension, and potentially respiratory failure 1
• In clinical studies with talquetamab, CRS was observed in 77-80% of patients at the recommended phase 2 doses, though most cases (all but one) were grade 1 or 2 in severity 2
• The American Society of Transplantation and Cellular Therapy (ASTCT) consensus criteria define CRS as "a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells" 1

Management of CRS with Headache

• For grade 1 CRS (which may include headache with fever ≥38°C), management includes supportive care with acetaminophen, cooling blankets, and IV fluids as needed 1
• If symptoms persist or worsen, tocilizumab (an IL-6 receptor antagonist) may be administered at 8 mg/kg IV (not to exceed 800 mg per dose) 1
• Siltuximab (an IL-6 inhibitor) has also been successfully used to manage CRS in patients receiving talquetamab, with resolution of symptoms within hours of administration 3
• For higher grades of CRS with more severe symptoms, additional measures including corticosteroids, intensive care monitoring, and vasopressors may be required 1

Distinguishing CRS-Related Headache from Other Neurological Toxicities

• It's important to distinguish CRS-related headache from immune effector cell-associated neurotoxicity syndrome (ICANS), which is another potential complication of T-cell redirecting therapies 1
• ICANS may present with more severe neurological symptoms including encephalopathy, aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, and seizures 1
• While headache alone is typically considered part of CRS, persistent or severe headache with additional neurological symptoms should prompt evaluation for ICANS 1
• Neurological consultation and additional workup including MRI and lumbar puncture may be warranted if ICANS is suspected 1

Monitoring and Prevention

• Patients receiving talquetamab should be monitored closely for symptoms of CRS, including headache, especially during the first cycle of treatment 2
• The risk of CRS is highest during initial dosing, which is why step-up dosing approaches are typically used with talquetamab 4
• Premedication protocols may be implemented to reduce the risk and severity of CRS symptoms 1
• Patients should remain within 2 hours of the treating center for 4-8 weeks post-therapy and should return to their treating center upon experiencing any toxicities, including headache with fever 1

Conclusion

Headache is a well-documented symptom of CRS in patients receiving talquetamab. When accompanied by fever and other characteristic symptoms, it should be recognized as a potential manifestation of CRS and managed accordingly with supportive care and specific interventions as needed based on severity.