TRANSCRIPT VIDEO ID 3650 I UMASS: Laura S Wood

Laura Wood: So it's important to recognize the fact that immune-related adverse events or irAEs can occur and be involved in any organ system. Patients may present or develop multiple irAEs throughout their course of therapy, and it's also critically important to recognize that these irAEs can develop or recur following the completion or discontinuation of their checkpoint inhibitor therapy. The goals of irAE management are really to focus on ensuring that the irAEs don't progress and lead to poor clinical outcomes in and of themselves. That they don't lead to poor outcomes owing to inappropriate, premature, or unnecessary discontinuation of therapy. And we've gained a lot of experience on how to manage these and the safety of reinitiation of therapy following the completion of steroid tapers. And we need to really look at cost, as we've talked about previously, those costs and unnecessary healthcare utilization due to ineffective, inappropriate, or insufficient management of these irAEs.


If you're not familiar with the Common Toxicity Criteria, the CTCAE criteria, it is a wonderful resource for all of your staff, whether you're in urology, oncology, or radiation. That really helps us all talk on the same level at the same point on adverse events. We use these to educate patients. What is mild, moderate, severe? When do we need to be informed of those adverse events so we can evaluate them and intervene appropriately? Just looking at diarrhea and colitis, it's important to understand and look at grade two or moderate. The distinguishing characteristic that says this is likely immune-related is colitis, blood, mucus, or abdominal pain.


So while grade two diarrhea is an increase in four to six stools over baseline, note to file, you need to have a baseline assessment of their bowel function. Any patient who has those symptoms of abdominal pain, mucus, or blood in the stool has the potential for colitis, irrespective of the frequency or consistency of their bowel movements. So this CTCAE criteria for assessment is very valuable. When we look at the KEYNOTE-057 study, diarrhea of all grades, colitis 2% of all grades, constipation 2%. So while I'm the diarrhea queen with the VEGF-TKIs and the checkpoint inhibitors in kidney cancer, we really need to also be aware of the constipation risk. Fortunately, we have no grade three or grade four of these toxicities in the KEYNOTE-057 study.


We need to look at whether etiologies are related to the underlying disease, comorbidities, or concomitant medications. And while I give you examples here for diarrhea, this really relates to any potential immune-related adverse event. We need to look at these underlying etiologies. Our dermatologic AEs need to be evaluated by a dermatologist because there are many other underlying etiologies for dermatologic changes.


Pulmonary symptoms, I use this as an example to really pinpoint the importance of educating your staff from the rooming nurse all the way through to your APPs. We're going to see these checkpoint inhibitors, which we have in other malignancies, being used in multiple settings in urology and urologic oncology in combination with radiation therapy as well. If your staff is familiar with the criteria for the different gradings, they're able to identify a patient who presents, or by the time they've called your office, presents with what is a grade three symptom, which is a higher level of alert and urgency with evaluation as opposed to grade one. So if we've educated our patients and our caregivers on what these guidelines are, it will help them inform us earlier, more appropriately, and make repeat phone calls if needed.


Again, referring back to KEYNOTE-057, 66% of patients developed an all-grade irAE, but only 13% had grade three or four. Interestingly enough, there are ones we're not usually looking for, such as hyponatremia. We see that as an adverse event with all of our checkpoint inhibitors. So hyponatremia needs to be monitored. Arthralgias, such as our patient. Arthralgias, myalgias, some of those more subtle irAEs, depending on the age of the patient, really need to be sorted out. There are also those serious but rare adverse events related to immunotherapy that we need to be aware of.


Type-1 diabetes. I talked to a patient on Monday; he was doing fine. I get a call from the wife on Thursday, four days later; he's in the ICU with diabetic ketoacidosis. Things can change quickly. Be aware, make sure your patients and caregivers are aware. Shared decision-making, as we've talked about earlier, we really need to make sure that patients understand; they want to be fully informed. The level at which they want to be informed is different. We have those individuals who read and investigate, and we need to be comfortable with having them bring the clinical trial data and the medical journal and be comfortable with having that level of conversation. We also need to be comfortable and encourage that patient or caregiver who wants to know nothing that we really need to be able to do that in order to honor their values and their preferences.


Include patient goals. What is it that you wish to do? Why do you choose not to do something or choose something else? Please include clinical trials. Explain to patients, yes, you may have to travel an hour and a half each way for clinic visits, but you have those options. The Lazarex Foundation is a very good foundation for financial resources for patients involved in clinical trials. Talk about early and late-onset irAEs even after completion. So if you're doing survivorship, irAE needs to be included in any patient who receives a checkpoint inhibitor.


And again, ongoing goals. What are their goals throughout therapy? Patients have toxicity; can we hold? Let's see how it goes. Re-infuse, and restart. Ultimately, we've really gained the importance of multidisciplinary care, whether you're the radiation oncologist, a urologist, or on the oncology team. Our multidisciplinary management is crucial to improve both clinical outcomes and efficacy, tolerability, and ultimately the quality of life for our patients, caregivers, and their families. Thank you so much.