From the Guidelines
The optimum fibrinogen level for CAR-T cell therapy patients should be maintained at ≥150 mg/dL (1.5 g/L), with replacement therapy recommended when levels fall below this threshold. This recommendation is based on the most recent and highest quality study, which provides guidelines for the management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy 1. According to the study, replacement of fibrinogen is considered in patients with a fibrinogen level below 150 mg/dL, particularly in those with bleeding complications.
Key Considerations
- Fibrinogen levels should be regularly monitored during CAR-T therapy, especially during cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) 1.
- Low fibrinogen levels increase the risk of bleeding, and prompt replacement is essential to prevent spontaneous hemorrhage, particularly intracranial bleeding, which can be life-threatening in CAR-T patients experiencing neurotoxicity.
- The study suggests using IL-6 antagonist with or without corticosteroids for patients with laboratory findings and bleeding, and critical care support for those with life-threatening conditions 1.
Replacement Therapy
- Cryoprecipitate is the preferred replacement product, typically administered as 1-2 units per 10 kg body weight.
- Fibrinogen concentrate (such as RiaSTAP) at 70 mg/kg can be used as an alternative when cryoprecipitate is unavailable.
- The goal of replacement therapy is to maintain fibrinogen levels above 150 mg/dL to prevent bleeding complications and ensure patient safety.
Clinical Implications
- Maintaining adequate fibrinogen levels is critical in CAR-T cell therapy patients, as it plays a vital role in hemostasis and prevents bleeding complications.
- Severe CRS can trigger disseminated intravascular coagulation (DIC), further depleting fibrinogen, and prompt replacement is essential to prevent life-threatening complications 1.
From the Research
Optimum Level of Fibrinogen in CAR-T Therapy
The optimum level of fibrinogen in Chimeric Antigen Receptor T-cell (CAR-T) therapy is not explicitly stated in the provided studies. However, the studies suggest that monitoring fibrinogen levels is essential in patients with moderate or severe Cytokine Release Syndrome (CRS) to avoid potentially fatal bleeding events 2.
Fibrinogen Replacement Guidelines
The study by 2 presents clinical guidelines for fibrinogen replacement during CRS-associated coagulopathy, which suggests that fibrinogen concentrate or cryoprecipitate replacement should be used when fibrinogen levels are below 1.5 g/L. Another study by 3 recommends continuous monitoring of coagulation parameters and adequate provision of fresh-frozen plasma or cryoprecipitate if the patient is evaluated to be at high risk for severe CRS.
Coagulation Abnormalities in CAR-T Therapy
Coagulation abnormalities, including hypofibrinogenemia, are prevalent complications in CAR-T-cell therapy 4, 5, 6. These abnormalities can range in severity from simple abnormalities in coagulation parameters to serious hemorrhage or disseminated intravascular coagulation associated with life-threatening multiorgan dysfunction.
Key Findings
- Hypofibrinogenemia requiring replacement was observed only in patients with severe CRS 2.
- A higher percentage of patients who required replacement were <10 years old, compared with those who did not require replacement 2.
- Coagulation disorders occurred mainly during day 6 to day 20 after CAR-T cell infusion 5.
- The changes in coagulation parameters were associated with high tumor burden, more lines of prior therapies, lower baseline platelet count, and especially cytokine release syndrome (CRS) 5.
Management of Coagulopathy
The management of coagulopathy in CAR-T therapy involves monitoring coagulation parameters, replacing fibrinogen, and using anticoagulant therapy 2, 3, 6. Early and proper interventions targeted at CRS-related coagulopathy can contribute to the control of side effects in CAR-T therapy 6.