Mark A. Socinski, MD: Let me ask Sandip, one of the things we haven’t talked about a lot is the [adverse] effects of immunotherapy [IO], although many of us believe that as a general class of drugs, these IO agents are generally quite well tolerated in this setting. What is the message to our audience regarding adverse events related to the immune system [IRAEs] and in their recognition and management? Do you have any golden pearls that you can share with us, Sandip?
Sandip P. Patel, MD: I think these therapies are remarkably effective immunotherapies that we have discussed, but they are not without toxicity, and the double-edged sword of the immune response is friendly fire against healthy tissue and you can achieve self-toxicities. immune. In lung cancer, the toxicity that is probably the most annoying in our practices is pneumonitis. Immune-mediated lung disease, it often mimics various other entities to which our lung cancer patients are particularly prone, whether it is COPD [chronic obstructive pulmonary disease] to burst; infection, especially the most recent with COVID-19; pulmonary embolism; disease course. So, these patients invariably have chest CT scans to try to gain a better understanding, and the problem with many immune system-related adverse events is that there isn’t a specific blood test that tells you that this is. ‘a phenomenon linked to the immune system. You will have a liver function test or a CT scan that will show something is wrong. You’re going to try to rule out everything else, but the problem with almost all of our immune system adverse events is that they are exclusion diagnoses. With that, you rule out other things, and you start therapy empirically.
My humble 2 ARI tips are, # 1, have a high index of suspicion. If the patient is more short of breath than usual or begins to have diarrhea, exclude Clostridioides difficile, but be prepared to treat it like immune colitis. The second is to start steroids early, especially after you’ve ruled out an infection, which you can often do quite quickly with a procalcitonin, for example. Or treat at the same time as steroids and antibiotics for a very severe case of, say, colitis while you wait for results and wait for specialist expertise because I have never seen anyone regret giving steroids too much. early. I’ve only seen people regret not starting steroids early enough. Then finally, there was a nice summary at ASCO [American Society of Clinical Oncology annual meeting]… Who reviewed what to do if steroids don’t work. I think the message is there if you have immune-related colitis which means you have ruled out C diff, which unfortunately can be common in this patient population, infliximab or another anti-TNF [tumor necrosis factor] can be effective. But beyond that, our options start to become increasingly potentially problematic for patients, including drugs that block T cells, such as mycophenolate. You can use drugs that block the movement of immune cells in normal tissue, like vedolizumab, and I think it gets really complicated at this point. But the only point I should make about steroids is that it’s not your 5 day COPD burst. If you are dealing with an immune system related adverse event, you want to have at least a 3 week steroid decrease, and probably closer to a month, maybe a little over a month, because if you don’t not, the likelihood of this immune effect returning from any related adverse event, whatever it is, is quite high.
Mark A. Socinski, MD: We presented data to the recent ASCO that a low intensity immune adverse event might be a good thing in this context. Of course this was also true on the scan control arm of IMpower150, 130, 132, so any thoughts on this? Because I agree with your comment that understanding the spectrum of toxicity can affect almost any organ and recognize that hopefully when it’s grade 1 or 2 it needs to be treated early and there. ‘prevent being 3 or 4. And that was sort of the message of this analysis.
Sandip P. Patel, MD: Absolutely, and it’s a great summary of a very complicated data set. I think the general theme of the studies you mentioned, as well as other analyzes, especially some retrospective analyzes, is that the development of an adverse event related to the immune system means that the immunotherapy affects the immune response. And as you raise the temperature, so to speak, of the immune system, hopefully more of that heat is directed to cancer, but some of it can also be directed to friendly organs, and so there is this correlation which I think has been seen in several databases. I’m not 100% there, but I think most of us have seen it, that most patients who develop ARIs are often the ones who benefit. This does not mean that you have to get any of these autoimmune toxicities to benefit from immunotherapy, but it does mean that for patients who develop an adverse event related to the immune system, the issue of reinjection often involves severity. of toxicity, how dangerous it was to life, how recoverable it was with immunosuppressive steroids. But if you also know that this patient who had this immune toxicity has a fairly good long-term prognosis, that means you can take a break. You can look with serial CT scans and see if the immune system took over the cancer and caused toxicity on the normal epithelium. I think this is probably where this dataset is most relevant to the clinical practice of most people.
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