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CAR T and BsAb Related AEs
Emergency Medicine Management of CAR T-Cell and Bispecific Antibody Therapy–Related AEs

Released: April 22, 2026

Brian Cameron
Brian Cameron, MD
Nathan Shapiro
Nathan Shapiro, MD, MPH
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Key Takeaways
  • Recognizing and managing CRS and ICANS in the emergency department in patients receiving CAR T-cell or bispecific antibody therapies is challenging due to symptom overlap with sepsis.
  • Management of CRS and ICANS follows consensus guidelines for grading assessments; however, until a diagnosis is established, patients should be initially treated for infection and stabilized, after which management should be guided by toxicity and grade of CRS and/or ICANS.
  • A multidisciplinary approach is recommended, and the managing oncologist should be contacted to help guide CRS and ICANS management while maintaining CAR T-cell or bispecific antibody therapy efficacy.

This expert commentary highlights key takeaways from a live educational event for emergency medicine professionals on recognizing and managing adverse events associated with CAR T-cell and bispecific antibody therapies in the emergency department, with a focus on cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), including expert answers to frequently asked questions from the live event.

CRS and ICANS: Onset, Grading, and Associated Symptoms

Bryan Cameron, MD:
In patients who receive CAR T-cell or bispecific antibody infusion as treatment for advanced/recurrent cancer or hematologic malignancy (ie, multiple myeloma or lymphomas), CRS may present 2-3 days after and most often occurs within the first 2 weeks, with later onset being less common. CRS is a systemic inflammatory response driven by cytokine release, producing symptoms that mimic sepsis, including fever, myalgias, hypotension, hypoxia, and potential organ dysfunction. Severity is graded from 1-4, with fever present in all grades and increasing levels of hypotension (from fluid-responsive [grade 2] to vasopressor-dependent [grades 3-4]) and hypoxia (from minimal oxygen support [grade 2] to mechanical ventilation [grades 3-4]) defining progression.

Similarly, ICANS may present in patients receiving CAR T-cell or bispecific antibody therapy. ICANS often follows CRS, but sometimes occurs independently, typically 4-6 days after treatment. It often lasts 14-17 days and may evolve from CRS. ICANS presents with a wide range of neurologic symptoms, including delirium, aphasia, confusion, lethargy, tremors, and seizures, which can progress to decreased consciousness, focal deficits, cerebral edema, or coma. Clinical manifestations often include impaired orientation, inability to follow commands, and early signs such as changes in handwriting. ICANS severity is graded using the ICE scoring tool with a 10-point cognitive assessment tool that measures progression from mild impairment (grade 1) to unresponsiveness and severe neurologic injury (grade 4).

CRS and ICANS: Presentation in the Emergency Department

Bryan Cameron, MD:
In patients who present to the emergency department, CRS commonly mimics sepsis (ie, with fever, hypotension, hypoxia, tachycardia, and flu-like symptoms) and, if untreated, can rapidly progress to organ dysfunction. ICANS presents with neurologic changes such as confusion, delirium, and aphasia, and may progress to seizures or unconsciousness. Because these conditions can overlap and evolve quickly, healthcare professionals in the emergency department must maintain a high level of suspicion and closely monitor for both systemic and neurologic deterioration. Patients presenting with these symptoms should be queried about a history of malignancy and any associated treatments received.

Management of CRS and ICANS in the Emergency Department

Bryan Cameron, MD:
CRS is managed by initially treating patients as potentially septic because infection cannot be completely ruled out in the emergency setting, while also considering recent infusion timing (especially within the first 2 weeks). Early management of CRS emphasizes supportive care and broad-spectrum antibiotics, with escalation based on severity. For example, fluids, supplemental oxygen, and tocilizumab should be given to a patient with grade 2 CRS, with considerations for high-dose steroids if there is no improvement with the aforementioned. ICU care should be given to patients with grade 3-4 CRS. It is also important to recognize that patients can deteriorate rapidly. Therefore, close monitoring is often required. Controlling toxicity should be balanced with preserving treatment efficacy when making care decisions.

Nathan Shapiro, MD, MPH:
Patients with combined CRS and ICANS often require both anticytokine therapy and immunosuppression, along with close monitoring and potential critical care support. Given the risk of rapid deterioration, healthcare professionals should maintain a low threshold for admission and use clinical judgment alongside established management protocols.

Involvement of the Oncology Care Team

Bryan Cameron, MD:
Management of CRS and ICANS requires close collaboration with the oncology care team members, who should be consulted early and frequently due to their specialized expertise. Oncologists play a pivotal role in guiding treatment decisions, particularly in balancing the use of steroids and tocilizumab, which can mitigate toxicity but may also reduce therapeutic efficacy. They can help provide support for stabilizing the patient regarding interventions based on severity and when to escalate with immunosuppressive agents like anakinra. This multidisciplinary approach ensures appropriate management while preserving the intended antitumor effects of therapy. Management is multidisciplinary, with early and ongoing oncology involvement critical to guide therapy, particularly for ICANS, where steroids are introduced earlier and more aggressively, and additional agents like anakinra may be considered in severe cases.

Frequently Asked Questions

How does infusion timing influence triage and emergency department diagnostic urgency?

Bryan Cameron, MD:
Initially, it is unclear whether the patient is septic or is experiencing symptoms of CRS or ICANS. Every patient should be treated promptly with antibiotics. If their blood pressure is low, they should be given IV fluids, and infection should be ruled out. Once the patient is stabilized and possibly treated with vasopressors, we then establish when they received a CAR T-cell or bispecific antibody infusion. Based on timing, we can establish whether there is a possibility that the patient is experiencing cancer therapy–related CRS or ICANS.

Can ICANS present without fever or hypotension, and how does that alter the workup?

Bryan Cameron, MD:
ICANS can present without fever, but it does not alter the workup or management. However, neurologic findings will still be present in patients experiencing cancer therapy–related ICANS with or without CRS.

What if a patient lacks documentation or their wallet card is not available?

Nathan Shapiro, MD, MPH:
Medical records will be 1 source of information. The second source is the oncologist. Between the patient, oncologist, and medical records, the appropriate information should be accessible.

When should the treating oncology group be contacted if a patient presents to the emergency department?

Nathan Shapiro, MD, MPH:
I think it depends on the local practice, but in general, these patients are at risk. They are undergoing very extensive treatments. In the absence of something like a laceration and depending on the local practice, I believe oncology should almost always be contacted while the patient is in the emergency department for acute care.

Where do emergency department workflows most often break down for patients?

Nathan Shapiro, MD, MPH:
It depends, but primarily on diagnosis and recognition. The key differential is determining whether the patient has an infection, CRS, or ICANS. This is not necessarily where the workflow most often breaks down, but this is the critical step.

How long does it take for CRS and ICANS to resolve?

Nathan Shapiro, MD, MPH:
With CRS, it can be a matter of days, but with ICANS, it can be weeks, and there is a range of residual challenges, such as short-term memory deficits, tremors, aphasia (difficulty speaking), and cognitive impairment, often called prolonged neurotoxicity. Steroid management depends on how long the patient is hospitalized, but longer-term steroids are an option.

Your Thoughts

What challenges in the recognition, grading, and management of CRS and ICANS have you encountered in the emergency department? Answer the polling question and leave a comment to join the discussion.

Visit the program page, download the slides from the live program, or watch an on-demand webcast to go deeper into educating yourself and your colleagues on this topic.

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For patients who present to emergency care with symptoms of sepsis or neurologic symptoms, how often do you consider cancer-related CRS or ICANS etiology?

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