By Eliana Baker and Addi Georgantzis, MSN, RN, AGPCNP-BC, OCN^®, BMTCN^®

On day 1 postinfusion, she developed grade 1 cytokine release syndrome for which she received tociluzimab per protocol. Her fevers persisted, and she received two additional doses of tociluzimab on days 2 and 3 post-IEC. 

On day 4, Mrs. Brown developed an altered mental status; the nurse notified the provider of her IEC score of 7. Mrs. Brown was diagnosed with grade 2 IEC-associated neurotoxicity syndrome (ICANS) and was started on dexamethasone 10 mg IV. 

For the next several days, she continued to receive dexamethasone for persistent ICANS, but her liver enzymes and ferritin levels continued to rise. The nurse noticed the uptrending lab values and thrombocytopenia and immediately notified the physician. 

What Would You Do?

IEC is a promising approach in cancer treatment that uses the immune system to target cancer cells. However, it may lead to a severe hyperinflammatory syndrome known as hemophagocytic lymphohistiocytosis (HLH). Understanding the use of IEC therapy and differentiating between CRS and IEC-associated HLH-like syndrome (IEC-HS) will optimize patient outcomes.  

IEC-HS and CRS share many clinical and laboratory features. Both conditions involve macrophage activation, with most moderate-to-severe CRS cases meeting HLH criteria. IEC-HS is a distinct hyperinflammatory syndrome independent from CRS and ICANS secondary to immune effector cell therapy. It is characterized by new or worsened cytopenias, rapidly rising ferritin levels, coagulopathy, and elevated hepatic transaminase levels. 

Although HLH-like manifestations are frequently observed in patients with severe CRS, IEC-HS onset is often delayed and manifests as CRS that is resolved or resolving. It should not be used to describe only manifestations of severe CRS. 

Monitoring should include daily complete blood counts with differential, LDH, coagulation parameters (prothrombin time, partial prothrombin time, international normalized ratio [INR]), and fibrinogen levels as well as assessment for renal and hepatic dysfunction. Check ferritin levels daily until they are less than 50% of peak, then monitor twice weekly until HLH resolves. Also monitor triglycerides, haptoglobin, C-reactive protein, fibrinogen, cytokine-3 panel, soluble IL-2, and interferon gamma, and assess patients for bacterial, viral, and fungal infections. 

Treatment for IEC-HS involves corticosteroids with or without anakinra or ruxolitinib. Other treatment options, such as low-dose etoposide or emapalumab, may be considered in refractory cases, although data for their use in IEC-HS are limited. Despite the established use of tocilizumab in CRS, tocilizumab and other IL-6–blocking agents have limited use in the treatment of IEC-HS without CRS manifestations.  

Supportive care includes managing cytopenias with growth factors; maintaining hemoglobin greater than 7 g/dl and platelet count greater than 50 cells x 10⁹/L in those with active bleeding or coagulopathy; and administering cryoprecipitate or fibrinogen products if bleeding occurs. Consider use of vitamin K for elevated INR. 

Mrs. Brown’s cancer care team discussed her case and recommended that she begin anakinra injections. Anakinra, an interleukin-1 blocker, is an off-label management for IEC-HS. Mrs. Brown returned home in stable condition three weeks after her initial IEC infusion. The care team scheduled an immediate outpatient follow-up within 24 hours of discharge from the hospital so they could continue monitoring her laboratory tests (e.g., complete blood counts, chemistry panel, ferritin, C-reactive protein) and watch for early signs of IEC-HS, ICANS, CRS, and HLH. The nurse educated the family and patient on medication adherence, follow-up compliance, and proximity to the cancer center. The nurse ensured the patient did not drive, received equipment to monitor vital signs at home, and had a caregiver with her 24 hours a day until she was at least 28 days postinfusion. 

Nursing assessment is critical immediately following IEC infusions. Patients with persistent CRS, worsening cytopenias, and elevated ferritin and transaminases need close monitoring for IEC-HS. The direct care nurse is at the forefront of patient care, and clinical assessment is imperative to ensure positive patient outcomes.