Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Clinical experience with checkpoint inhibitor-associated immune-related adverse events
3:30 minutes.
TRANSCRIPTION:
DR GALSKY: One of the aspects to these drugs that I think warrants a little bit of consideration is the fact that when results are presented from clinical trials, usually with toxicity data, what’s reported are adverse events that occur in greater than or equal to 5% of the population. And I think we might be missing rare side effects that are only occurring in 1 to 2 patients. And I think about this the same way you think about these rare genetic alterations when you look at mutation data. There are rare mutated genes, which might be clinically important. But it’s not really spoken about, because it’s hard to interpret. We don’t know if those are meaningful. And I think, similarly, with some of this long tail in terms of adverse events, it’s hard to sort out sometimes if it’s drug related or not. But I think we are missing a number of immune-related adverse events that are only occurring in a few patients. DR LOVE: Any, in particular, that you have in mind or that you’ve observed? DR GALSKY: So I’ve really observed immune-related adverse events that mimic the spectrum of autoimmune diseases. So things like polymyalgia rheumatica, really classic, classic symptoms for that, classic signs for that, and seem to temporarily be associated with starting immune checkpoint blockade, got better with steroid management, so these sorts of things. DR LOVE: It kind of ties into also the question, which I’ve been asking people for all different tumor types. And I don't know how often it occurs, which is people with prior autoimmune diseases. DR GALSKY: Yes. DR LOVE: And I’m curious. When you know about it, like polymyalgia rheumatica — I don't know. Maybe they had it and never realized it. I don't know. But do you have any patients who’ve had Crohn’s disease or other autoimmune diseases? And how did you deal with it in that situation? DR GALSKY: I think it’s a great point in terms of whether or not some of these were subclinical prior to initiation of these treatments. Because the vast majority of clinical trials have excluded patients with these conditions, the experience is obviously quite limited. I have had no experience — I have not had experience treating patients with inflammatory bowel disease yet. I would say that the frequency of some of these diagnoses, inflammatory bowel disease, even psoriasis, is markedly higher than I would have predicted before, or looking for these diagnoses with the availability of these drugs. So I think ultimately we will have to better understand what’s happening with treatment in these patients, because these diagnoses are not so uncommon. I have treated patients with psoriasis. I have treated patients with rheumatoid arthritis. I’ve been lucky so far. There is some published data, of course, even though it’s retrospective, with ipilimumab in patients with preexisting autoimmune diseases, showing that there does seem to be a flare in those diseases. But in most patients you can get away with it, with treating those flares, and so I think it’s a work in progress. |