Managing Adverse Events in Patients Taking First-line Therapy for Metastatic Melanoma

Discussion centered around planning for, managing, and overcoming adverse effects in the first-line systemic therapy setting for melanoma.

Hussein Tawbi, MD, PhD: In terms of approaches to managing adverse events for patients with first-line metastatic melanoma so again, if we treat them with combination immunotherapy, I really focus very much on educating the patients on what to expect and what are the types of toxicities and kind of really making sure that they have direct access to our team and to also inform them of what are the specific signs that they need to bring up to our team. I also make a point that most of these toxicities develop over days to weeks and not typically over minutes to hours so really encouraging those patients to reach out early is very important. Again, since we see those patients every three weeks or so we may be able to detect some of those side effects even if the patients did not specifically speak of them like LFT elevation is not something that patients are typically symptomatic of. For those reasons, we try to act on side effects as soon as we observe them. Ideally, if we start having grade one or grade two toxicities, ideally you would hold the next treatment. You don't proceed with treatment so that you don't escalate the toxicity with immunotherapy. Then if it reaches grade three or four, that's when you consider steroids first. Then sometimes for more severe toxicities or refractory to steroid toxicities, we consider anti-TNF agents or anti-IL6 agents, and other agents like vedolizumab for colitis. If we were treating patients with targeted therapy, obviously the approach is different with targeted therapy. Again, education is always very important and kind of making sure that the patients are very much aware of what to expect. Also with targeted therapy, there's a lot of value to short interruptions so a day or two off of the treatment, sometimes requiring dose reductions but generally, again, the experience with both approaches are that we can really spare our patient's life-threatening toxicities or manage them relatively early so that they're not a threat to their lives. The incidence of grade five toxicity or deaths related to toxicity is quite limited and almost non-existent if the patients were managed properly and early on.

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