Expert Spotlights the Importance of the New SITC Guideline on Managing IRAEs

Marc Ernstoff, MD

The recent publication of a new clinical practice guideline from the Society of Immunotherapy of Cancer (SITC) on how to manage immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors has offered much-needed insight for treating oncologists.

Research has shown that although fatigue and dermatological toxicity are the most common AEs, more severe issues like gastrointestinal or neurological toxicities are of concern for these patients. Research has also suggested that these irAEs can impact outcomes.

In a press release, Julie R. Brahmer, MD, co-chair of the SITC Immune Checkpoint Inhibitor-related Adverse Events Expert Panel said: "Checkpoint inhibitors have transformed cancer care, yet these unique therapies can cause toxicities that are quite different than what is seen with traditional anti-cancer treatments and our understanding of irAEs is con. The Expert Panel considered the latest evidence available in the literature as well as their own vast wealth of experience in treating irAEs to develop this guideline, which will provide clinicians with the most current thinking on toxicity management, in order to safely use checkpoint inhibitors and provide the best-possible outcomes for patients."

The guideline provides recommendations for identifying irAEs, following up on the toxicities, and mitigating them.

In an interview with Targeted Oncology™, Marc Ernstoff, MD, chief of the ImmunoOncology Branch in the Division of Cancer Treatment and Diagnosis, Developmental Therapy Program at the National Cancer Institute, and co-author of the new guideline, discussed the significance of the recommendations and what doctors should take away from the publication.

TARGETED ONCOLOGY™: What is the importance of these recommendations? Why were they developed?

Ernstoff: Over the past decade or so, the role of immunotherapy has expanded dramatically. Particularly with the introduction of immune checkpoint inhibitors, such as nivolumab [Opdivo], pembrolizumab [Keytruda], and ipilimumab [Yervoy], the use of these agents is now in many, many different cancers. And the spectrum of AEs associated with immune checkpoint inhibitors is unique and differs dramatically from the standard chemotherapy or radiation, and it's critical that the society as well as other societies really put forward understanding the mechanism and treatment of these AEs.

What is your key takeaway from this new guideline?

I think the general takeaway is one to recognize that the AEs of these agents are different and unique. That identification and diagnosis of the toxicity therefore becomes important to recognize the treatment or the management of the toxicities are also different than other standard therapies. And it needed to be outlined for individuals and that the toxicity profile is such that it's not always immediate. And not necessarily doesn't necessarily follow immediately upon therapy but can be delayed and that the management of the AEs many times requires multi specialties.

In relation to the different type of irAEs, which are the most concerning? How are outcome impacts by these AEs?

Independent of whether the AEs are gastrointestinal or skin or central nervous system, they are the grading or the variation of the seriousness of the AEs are significant, and that the life-threatening tie types of toxicities associated with each of the organ that can be involved is critical because it could be life threatening. So, though exceedingly rare, bullous formation in skin toxicity could be potentially life threatening, if not recognized early manage, clearly cardiomyocyte is to do development of type one diabetes can be life threatening, if not identified. And associated. Gi toxicity, which is usually the diarrhea associated with colitis, if not recognized can cause perforation and catastrophic events. So, it's important to recognize that while many of these agents, particularly single agent therapies are well tolerated in general, that physicians shouldn't be lulled into complete complacency in in querying patients and making sure they are followed closely for the development of the AEs.

There’s a portion of the guideline that mentions about patients with autoimmune disease. Would you say this is 1 of the subgroups in whom immune-related AEs are most harmful?

Current research is directed at trying to identify patients at risk for AEs. Clearly, patients that had an underlying autoimmune disease, some increased risk related to that auto immune illness. And while it’s not an absolute contraindication, the management of those patients really need to be done very carefully, both by the treating physician treating oncologist as well as in collaboration with their rheumatologist or other physician that's managing their there are other illnesses. Typically, people that have inactive autoimmune have a history of autoimmunity Be careful, but usually want to follow-up with those patients. Patients that have active autoimmune disease that require immune suppression are much more difficult to manage. And, again, you know, needs to be weighed carefully between risk of dying for their cancer and risk of contributing aggravation or autoimmune disease. So, as these agents are moving into adjuvant therapies, that risk benefit ratio may be in favor of not treating patients with active advanced disease, where their cancer could be, and would be life threatening. If not effectively treated, that balance of risk and benefit cages. So, that all must be weighed carefully.

What is the role of multidisciplinary care in mitigating these irAEs?

The first identification of the event and the severity of the event many times requires a collaboration with a multidisciplinary team. So, for example, uveitis can a clearly needs to be evaluated by an ophthalmologist with the appropriate eye examination. And many times. these symptoms of uveitiscan be minimal, while the underlying pathway pathology of the uveitis

can be very severe, and if not recognized, can lead to blindness. So, recognizing the signs early in the development of toxicity, whether it be gastrointestinal or cardiac or neurological, that collaboration with appropriate subspecialty, is critical in managing that AE and minimizing the immune suppression agents that are being used.

What do oncologists need to know about this new guideline?

The takeaway is that it's potentially a complicated area of managing AEs and in recognizing these AEs. SITC as an organization is leading a webinar education process to help the community understand these guidelines more effectively.

I think the take home message is that that one has to recognize that this is a different therapy that has its unique AEs and that being able to use these drugs effectively, one has to be able to recognize and manage those toxicities.

_Reference:

_{Society for Immunotherapy of Cancer publishes clinical practice guideline on immune checkpoint inhibitor-related adverse events. News release. July 14, 2021. Accessed August 31, 2021. https://prn.to/3kE0cFY}