Inpatient and Outpatient Management of Immune-Related Adverse Events

Inpatient and Outpatient Management of Immune-Related Adverse Events Posted By:
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Immune checkpoint inhibitors (ICIs) carry the unique risk of a highly unpredictable class of toxicities called immune-related adverse events (irAEs). In some instances irAEs are mild and can be managed in the outpatient setting, but more severe cases often warrant hospitalization. In this commentary, Jordan McPherson, PharmD, MS, BCOP and Alexa Basilio, PharmD, BCOP discuss factors for deciding when a patient experiencing an irAE should be admitted to the hospital and how pharmacists in the inpatient and outpatient settings can best collaborate to optimize patient outcomes.

Deciding When to Admit a Patient Who Is Experiencing an irAE
Three things should be considered when deciding if a patient who is experiencing an irAE should be managed in the inpatient or outpatient setting: (1) the grade of the toxicity, (2) how clinically stable the patient is, and (3) the complexity of the irAE and the number of tests required for a full workup. Grading of irAEs is critical and should be the first step in establishing a management plan. The National Comprehensive Cancer Network, American Society of Clinical Oncology, Society for Immunotherapy of Cancer, and European Society of Medical Oncology have each published consensus guidelines for managing irAEs. These guidelines are freely available and should be referenced when a patient is experiencing an irAE. Patients requiring oral and topical steroids usually can be managed in outpatient clinics, whereas those requiring IV steroids typically need to be hospitalized. Those who are clinically stable may be managed in the outpatient setting for select high-grade toxicities, such as rash, hepatitis, arthritis, or hypophysitis. For example, patients with grade 3 aspartate or alanine transaminase elevation may be appropriately managed in the outpatient setting using oral prednisone with laboratory monitoring every few days. For irAEs that are more complex and require extensive or urgent workup, inpatient management is likely necessary. Examples of these include colitis, pneumonitis, nephritis, myocarditis, among others.

The inpatient setting offers the benefits of expedited multidisciplinary evaluation, faster access to laboratory testing and imaging, and closer monitoring as compared with outpatient settings. For example, colonoscopies for patients with severe diarrhea/colitis are challenging to perform urgently in an outpatient setting, especially in systems with limited resources. In the inpatient setting, healthcare professionals can work together to quickly address any complications that may arise. If a patient is unresponsive to initial treatment, secondary agents may be employed, or steroid dosing may be escalated. 

With some toxicities, it can be difficult to distinguish if a patient is experiencing an irAE vs a symptom associated with their underlying cancer—for example, suspected pneumonitis in a patient with a thoracic malignancy receiving an ICI may be an irAE, a complication of radiotherapy, or a sign of disease progression. In these challenging cases, a multidisciplinary approach should be taken to weigh the risks and benefits of steroid treatment prior to a definitive diagnosis and to ensure that a thorough workup is done and an accurate diagnosis is made. Together, the entire clinic team can help to decide on the best way to progress in complex cases. A multidisciplinary approach has become increasingly important as new immune checkpoint inhibitors are approved and cancer-related indications are added. We now have 11 FDA-approved ICIs for cancer-related indications, and some are being used in combination with targeted therapies. Combination regimens have a more complex safety profile, making a multidisciplinary approach helpful for determining which agent may be causing toxicity and informing the best management strategy.

Ensuring a Smooth Transition Between the Inpatient and Outpatient Settings
Open communication between the care team in the inpatient and outpatient settings can help ensure a smooth transition for patients with irAEs. Prior to admission, the care team in the ambulatory clinic can provide insight for ruling out other diagnoses by utilizing the patient’s pertinent medical history and oncology treatment history.  After admission, when the patient transitions back to outpatient care, the inpatient care team can provide information on which treatments were used during hospitalization and how the patient responded to therapy. In many instances, patients are stabilized and released from the hospital before their irAEs resolve to grade 1. The care team in the outpatient care setting has the responsibility to follow up with the patient after discharge and ensure that the steroid taper is appropriate based on how the irAE resolves. Nursing and pharmacy teams can help to guide steroid tapers and provide guidance on whether a patient will need a typical 4-week or a more prolonged 6- to 8-week taper. Furthermore, they can provide guidance on supportive care medications while on the steroid taper. As a patient transitions between the inpatient and outpatient settings, it is also important for each care team to directly collaborate with the patient’s primary oncologist, as they are most familiar with the clinical needs and goals of care for the patient.


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Filed under: Oncology/Hematology , NPs & PAs

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