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CE

Practical Insights Into Managing Immune-Related Adverse Events in Cancer Patients

  • Authors: Kelly Brassil, PhD, RN, AOCNS
  • CE Released: 5/24/2019
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 5/24/2020
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Target Audience and Goal Statement

This activity is intended for hem/onc specialists, pulmonologists, and emergency medicine physicians.

The goal of this activity is to present practical information and strategies to oncology nurses for counseling and monitoring patients receiving immune checkpoint inhibitors for prompt recognition and management of immune-related adverse events (irAEs).

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Recommended strategies for monitoring and managing irAEs by type and severity
  • Have greater competence related to
    • Providing patients with critical information and tools that help them recognize potential irAEs and seek additional care when necessary


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Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


Faculty

  • Kelly Brassil, PhD, RN, AOCNS

    Director, Nursing Research and Innovation
    The University of Texas MD Anderson Cancer Center
    Houston, Texas

    Disclosures

    Kelly Brassil, PhD, RN, AOCNS, has disclosed the following relevant financial relationships:
    Received grants for clinical research from: AbbVie Inc.; Astellas Pharma; Genentech, Inc.

Editor

  • Elaine Hamarstrom, PhD

    Medical Education Director, Medscape, LLC

    Disclosures

    Disclosure: Elaine Hamarstrom, PhD, has disclosed no relevant financial relationships.

  • Tristin Abair, PhD

    Medical Writer, Medscape, LLC

    Disclosures

    Disclosure: Tristin Abair, PhD, has disclosed no relevant financial relationships.

Nurse Planner

  • Amy Bernard, MS, BSN, RN-BC, CHCP

    Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Disclosure: Amy Bernard, MS, BSN, RN-BC, CHCP, has disclosed no relevant financial relationships.


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  • Awarded 0.25 contact hour(s) of continuing nursing education for RNs and APNs; 0.25 contact hours are in the area of pharmacology.

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CE

Practical Insights Into Managing Immune-Related Adverse Events in Cancer Patients

Authors: Kelly Brassil, PhD, RN, AOCNSFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CE Released: 5/24/2019

Valid for credit through: 5/24/2020

processing....

The goals of continuing medical education (CME) and professional development are to acquire and retain knowledge that will enhance clinical practice and improve patient outcomes.

What are the best practices for monitoring patients treated with an immune checkpoint inhibitor in order to quickly identify immune-related adverse events?

Kelly Brassil, PhD, RN, AOCNS: As cancer therapies continually evolve, immunotherapy is emerging as an investigational and standard of care treatment for diverse malignancies. With an increasing number of FDA-approved indications used as single agent or combination therapies, a greater number of patients are being treated with and are survivors following checkpoint inhibitor-based therapies.[1] While immunotherapies are extending life for previously progressive disease, they are accompanied by various acute and chronic immune-related adverse events (irAEs). Nurses in diverse roles and practice settings are pivotal in the assessment, early recognition, and management of these irAEs. An important first step to successful management is knowledge of the evidence-based resources available to guide timely and effective clinical care.

Unlike traditional cancer therapies such as radiation or chemotherapy that result in specific systemic toxicities, checkpoint inhibitor-associated immune activation leads to inflammatory responses that can impact organ systems throughout the body. The most common irAEs occur in the gastrointestinal tract, skin, liver, and endocrine glands; less common toxicities occur in the hematologic, musculoskeletal, pulmonary, and cardiovascular systems.2 These toxicities differ based on the type of checkpoint inhibitor, with anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 therapies more commonly associated with colitis and hypophysitis and anti-programmed death (PD)-1 therapy with pneumonitis and thyroiditis (Table 1).[1,3-5] Immune-related adverse events may occur acutely or chronically over a period of weeks to months following treatment initiation.[2] Late effects can also occur, even after the discontinuation of therapy, although it is not currently suggested that treatment over an extended period of time results in an increased incidence of irAEs.

Table 1. Select Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors[1,3-5]

 

CTLA-4 Inhibitors

PD-L1 Inhibitors

PD-1 Inhibitors

(Grade 3 or greater)

Ipilimumab

Tremelimumab

Atezolizumab

Avelumab

Durvalumab

Cemiplimab

Nivolumab

Pembrolizumab

Colitis

8%-10%

(5%-6%)

nd

< 1%

(< 1%)

1.5%

(0.4%)

1.3%

(0.4%)

0.9%

(0.4%)

1%-3%

1%-2%

(1%-2%)

Hypophysitis

2%-3%

(2%-3%)

2%

(1%)

<1%

(< 1%)

< 1%

nd

0.2%

(0.2%)

< 1%

<1%

(<1%)

Hepatitis

< 1%

(< 1%)

1%

(1%)

1%-2%

(1%)

0.9%

(0.7%)

1.1%

(0.7%)

2.1%

(2.1%)

1%-2%

1%-2%

(<1%)

Skin toxicities (pruritis/rash)

25%-34%

(< 1%-3%)

30%-34%

(1%-2%)

12%-15%

(< 1%)

< 1%

3%-4%

(0%)

15%-25%

(0%-1.2%)

30%-34%

11%-21%

(1%-2%)

Pneumonitis

< 1%

(< 1%)

nd

2.6%

(< 1%)

1.2%

(0.5%)

2.3%

(0.5%)

2.4%

(0.9%)

1%-5%

4%-6%

(1%-2%)

Hypothyroidism

1%-2%

(< 1%)

5

(1%)

2%-4%

(< 1%)

5%

9.6%

6%

(0.2%)

4%-5%

8%-10%

(<1%)

Hyperthyroidism

0%-2%

(< 1%)

2

(1%)

1%

(< 1%)

0.4%

8.1%

1.5%

(0.2%)

0%-3%

3%-4%

(<1%)

Abbreviations: nd = not determined; PD-1 = programmed death-1; PD-L1 = programmed death ligand 1.

We are fortunate to have several guidelines on how to best monitor patients for irAEs from the American Society of Clinical Oncology (ASCO®), National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Society for Immunotherapy of Cancer (SITC).[6-8] It is recommended that monitoring begin at the time of initiation of immunotherapy and continue throughout treatment. For patients on active treatment with checkpoint inhibitors, any new complications should be assessed as if related to therapy and be evaluated with the appropriate diagnostic workup, radiologic imaging, laboratory testing, etc. to allow differential diagnosis of symptoms.[6] This assessment is pivotal to early and appropriate intervention, as irAEs are often treated differently from other types of complications with similar presentations. Patients often experience symptoms in-between clinical assessments, so it is crucial to provide patient education on potential side effects and partner with them to ensure timely reporting of symptoms. Nurses may utilize diverse assessment approaches both in person and via telehealth to promote early identification of symptoms and timely coordination of assessment and management.[9]

You mentioned guideline recommendations, can you tell us what the recommendations are for managing irAEs once one has been identified?

Dr Brassil: Each guideline uses a unique approach to the organization of management recommendations, with ASCO/NCCN published by system; SITC published by disease type; and ESMO published by system with further detail by disease class.[6-8] The first step to successful treatment is appropriate grading of the presenting toxicity, with the Common Terminology Criteria for Adverse Events (CTCAE v5.0) utilized for these purposes.[10] The majority of irAEs present as grade 1 or 2, with some progressing to grade 3 or 4. Generally patients presenting with grade 1 toxicity may be managed with close observations or corticosteroids, often while continuing treatment. Progression to grade 2 toxicity typically requires dose interruption and introduction or dose escalation of steroids, while grade 3 or higher toxicity leads to progression to high-dose steroids or the introduction of immunomodulators such as infliximab.[6-8,11] Immune checkpoint inhibitors may be re-introduced when symptoms return to grade ≤1, although more serious adverse events and specific patient factors may preclude re-initiation of therapy even if symptoms diminish to grade 1.[6] Permanent discontinuation is generally suggested for patients experiencing grade 4 toxicity.

An important consideration when utilizing the available irAE guidelines is that the evidence upon which they are based continues to evolve as additional agents are approved and explored in combination with other cancer treatments. The guidelines are also informed by a consensus of experts based on their clinical experience, which can introduce substantial variability. Ultimately, the use of the existing guidelines should be balanced with the policies, procedures, and resources of the specific practice environment.

Timely management can be challenging when irAEs present with similar symptoms to other more commonly observed presentations. Pneumonitis, a relatively rare but potentially fatal complication, may occur in combination with or distinct from an underlying pneumonia, making it potentially difficult to diagnose.[12] Whereas pneumonitis is caused by an inflammatory response triggered by checkpoint inhibitor therapy, pneumonia results from a bacterial, viral, or fungal infection.[13] Both may present with shortness of breath and possible fever, though pneumonia is diagnosed with chest x-ray and blood and sputum culture, while pneumonitis requires computed tomography (CT), pulmonary function test, and biopsy. These distinctions are important since pneumonitis is treated with steroids and pneumonia is treated with the appropriate anti-microbials. The risk of misdiagnosis can result in ineffective treatment that may lead to progression of the underlying irAE.

What are the best practices for counseling patients who are being treated with an immune checkpoint inhibitor?

Dr Brassil: Education for patients and their caregivers is pivotal to ensure successful monitoring and management of irAEs. Patients may identify any cancer treatment as chemotherapy; therefore, education about the distinction between chemotherapy and immunotherapy and their unique toxicities is important. Immune-mediated AEs are driven by distinct mechanisms and are often more challenging to manage compared to those associated with traditional chemotherapy. For instance, while chemotherapy-induced diarrhea and immunotherapy-related colitis may both be treated with anti-diarrheal medications such as loperamide, immune-related colitis may also require steroid-based management with progression to infliximab at grade 3 or higher.[6] Patients need to be able to effectively communicate with non-oncology-based providers so symptoms can be quickly recognized as immunotherapy-related and appropriately addressed. Providers should reinforce the importance of identifying and reporting signs and symptoms as soon as they occur.[14] Patients are sometimes tempted to wait until symptoms are severe before reporting adverse events, resulting in progression of toxicity grade. Patients should also be educated about the potential for both acute and delayed toxicity, which may occur months and even years following treatment and can include an ongoing risk for opportunistic infections.[6,9] Use of toxicity monitoring documents such as journals or online trackers may also be helpful for patients to monitor for changes in symptoms.[15]

The 44th Oncology Nursing Society (ONS) Annual Congress was held recently. Were there any abstracts on irAEs that you would like to highlight?

Dr Brassil: Immunotherapy and toxicity management were a major focus of sessions and posters at the 44th annual Oncology Nursing Society Congress held in Anaheim in April 2019. A pre-conference presentation by Krista Rubin from Massachusetts General Hospital Cancer Center and Laura Wood from Cleveland Clinic Taussig Cancer Center provided a comprehensive overview of immunotherapy indications and toxicity management for nurses in a joint session co-hosted by SITC.[16] They followed with an additional session on side effect management focused on the SITC, ESMO, ASCO®, and NCCN guidelines. Posters presented during the congress addressed symptom management in patients receiving immunotherapy, the use of pocket cards to support patient communication with healthcare providers regarding the adverse events associated with immunotherapy, and the development of an immunotherapy standardized nursing assessment protocol, I-SNAP, as a screening tool for nurses to use to quickly identify irAEs and intervene.[17,18]

Do you have any specific suggestions for your community-based nursing colleagues regarding how to best manage irAEs in their practice?

Dr Brassil: An important aspect of community-based oncology care is recognizing that patients may present with symptoms of irAEs at a variety of locations, including community-based clinics, emergency rooms, and primary care practices. Nurses practicing in non-oncology settings are particularly important to ensuring safe and effective care of patients on checkpoint inhibitor therapy. Nurses in primary care, emergency, and community clinics are well-positioned to identify potential toxicities as patients present in those settings with symptoms.[19] It is critical that nurses from all practice settings work as a team to collaboratively support patients treated with immune checkpoint inhibitors. Organizations such as the ONS and other sources are seeking to bridge this gap across various care sites by developing resources and online tools.[20,21] Pocket cards can be carried in a wallet or purse and assist patients in communicating what therapies they are receiving in any practice setting, informing providers of the potential associated toxicities. It is then up to nurses and other healthcare professionals to remain aware of how to monitor and manage these adverse events to provide patient-centered care. Nurses in community and non-oncology practice settings must also remain aware of the best point of referral for patients experiencing irAEs associated with checkpoint inhibitors. This provides seamless care delivery and ensures that all members of the patient's healthcare team are aware and involved. Nurses are pivotal in early identification of irAEs in the oncology treatment setting and beyond. Utilizing evidence-based guidelines to guide assessment and management can support safe, timely, and effective patient management across care settings.

This transcript has been edited for style and clarity.

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