Resource Spotlight: Immune-related adverse events due to immune checkpoint inhibitors

October 24, 2023
 

Written by Huy Pham

This article was written and researched by a CSHP student member for Interactions, our biweekly newsletter. Crafting these pieces not only helps students gain in-depth knowledge of specific conditions, treatments, and resources, it also helps them hone their skills in research, critical appraisal, evaluation, synthesis, and writing – all of which will serve them well in clinical practice. The Professional Practice Team works with the student to select topics that are of interest and utility to both the student and to you, the reader. We hope you enjoy this piece by one of our future colleagues! Let us know what you think: If you would like to provide any comments or constructive feedback for our students, please email us at practice@cshp.ca

Background 

Immune checkpoint inhibitors are a class of immunotherapy that are used in the treatment of various cancers including lung cancer, melanoma, and colon cancer. There are currently eight immune checkpoint inhibitors marketed in Canada. The side effects of immune checkpoint inhibitors are collectively called immune-related adverse events and can affect any organ or organ system. The appropriate management will depend on the severity of the immune-related adverse event and the organ/organ systems affected. This “Resource Spotlight” contains links to tools and resources that pharmacy professionals can use to learn more about immune-related adverse events and how to manage them. To learn more about immune-related adverse events, check out CSHP's recent Clinical Pearls on immune-related adverse events due to immune checkpoint inhibitors. 

Canadian Guidelines and Healthcare Resources 

Cancer Care Ontario is a provincial agency responsible for providing healthcare professionals, organizations, and policy-makers with up-to-date knowledge and tools to support them with the prevention of cancer and the delivery of high-quality care in Ontario. They developed monographs for seven immune checkpoint inhibitors  that are marketed in Canada (ipilimumab, nivolumab, cemiplimab, avelumab, durvalumab, pembrolizumab, atezolizumab). In addition, Cancer Care Ontario has an Immune Checkpoint Inhibitor Side Effect Toolkit with toxicity algorithms to guide clinicians in determining the best course of treatment depending on the affected organ systems. The toolkit also contains a template for wallet cards and letters to notify healthcare providers that the patient is on immunotherapy, as well as a medication information sheet that can be given to patients to inform them about immunotherapies.

Cancer Care Alberta has created a guideline on the recommended strategies for prevention, anticipation, detection, and management of immune-related adverse events due to immune checkpoint inhibitors. The guideline is sectioned by organ systems and provides tables to help assess the severity of immune-related adverse events.

The Immune-Mediated Pathophysiology & Clinical Triage (i-MPACT) podcast is a ten-episode series created from the collaboration of Alberta Health Services, the Alberta Cancer Foundation, and Bristol Myers and Squibb. This series focuses on patient care with regards to immunotherapy such as immune checkpoint inhibitors with an emphasis on proactive and longitudinal care, the pathophysiology of immune-related adverse events, and toxicity management strategies.

BC Cancer has a comprehensive cancer control program that encompasses the entire spectrum of cancer care, from the prevention and screening of cancer to supportive and palliative care. BC Cancer provides protocols for healthcare professionals to use to guide the management of immune-related adverse events as well as a patient handout outlining the common and serious side effects of immune checkpoint inhibitors. Monographs may be found on the BC Cancer’s webpage. In addition, they have print-out wallet cards that patients in B.C. can carry to alert other clinicians that they received immune checkpoint inhibitor therapy.

The Canadian Association of Pharmacists in Oncology (CAPhO) is the membership-based national advocacy organization for the field of oncology pharmacy, acting as a resource centre to support pharmacists with providing optimal care for cancer patients. One of these resources is their CAPhO Connection Podcast, a recent episode of which covers the role of the pharmacist in immune checkpoint inhibitor management. Topics discussed includes the wide spectrum of adverse events associated with immune checkpoint inhibitors, the five pillars of management as described by an article in the Annals of Oncology by Champiet et al(“Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper”), and clinically relevant pharmacodynamic drug interactions associated with immune checkpoint inhibitors.

International Guidelines and Healthcare Resources 

The Immuno-Oncology (IO) Essentials Initiative is an organization dedicated to improving the health outcomes of patients receiving immunotherapies by providing healthcare professionals with the information needed to approach immune-related adverse events in an optimal manner. They also aim to empower patients by educating them to actively participate in their therapy in the context of immune-related adverse event recognition and management. The Immuno-Oncology Essentials Initiative curates content by country including a page for Canada. Their website has a library of videos detailing immune-related adverse events as a whole and in the context of specific cancers. They also have toolkits on the individual immune checkpoint inhibitors (as well as one on an oncolytic viral immunotherapy) and single-page Care Step Pathways documents to aid with the assessment of the presence and severity of immune-related adverse events and management strategies.

The American Society of Clinical Oncology released an update2 to their 2018 guideline on the management of immune-related adverse events due to immune checkpoint inhibitor therapy. The guideline contains tables that outline the work-up and evaluation of a patient presenting with an immune-related adverse event, the criteria for grading and management strategies, as well as a table of possible therapeutic alternatives for steroid-refractory immune-related adverse events. There is a complementary article3 that focuses on the ten most common immune-related adverse events secondary to immune checkpoint inhibitors and how they are managed. The guideline is also accompanied by an interactive tool to help with creating a comprehensive care plan for the immune-related adverse event.

The Society for Immunotherapy of Cancer is an organization that seeks to advance the science, development, and application of immunotherapies to improve the health outcomes of cancer patients. They have a guideline4 to aid with clinical decision-making for patients’ immune-related adverse events and a library of webinars and modules on their management, and patient resources to help patients understand immunotherapies and their use as cancer treatment.

The European Society for Medical Oncology is a professional organization for medical oncology with over 28,000 members from over 160 countries. They have released a clinical practice guideline5 that outlines their recommendations for the assessment, diagnosis and treatment of toxicities secondary to immunotherapy. The guideline contains treatment algorithms to guide one’s approach depending on the severity of the toxicity.

References

  1. Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F, et al. Management of immune checkpoint blockade dysimmune toxicities: A collaborative position paper. Ann Oncol. 2016 Apr;27(4):559–74.
  2. Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021 Dec 20;39(36):4073–126.
  3. Schneider BJ, Lacchetti C, Bollin K. Management of the Top 10 Most Common Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy. JCO Oncol Pract. 2022 Jun;18(6):431–44.
  4. Brahmer JR, Abu-Sbeih H, Ascierto PA, Brufsky J, Cappelli LC, Cortazar FB, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021 Jun;9(6):e002435.
  5. Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Dec;33(12):1217–38.