Case-specific Recommendations for the Treatment of 47-Year-Old Woman with Metastatic Melanoma

Revisiting the patient case study, Dr Hussein Tawbi shares how he might approach systemic first-line treatment in this situation, with a focus on limiting drug toxicity.

Hussein Tawbi, MD, PhD: As we consider first line treatments for patients with metastatic melanoma like our 47-year-old lady, there are several factors that we take into account. I have to say that even as we reviewed the DREAMseq study, for instance, it was interesting that ipilimumab and nivolumab first was superior to dabrafenib and trametinib first so the 20% overall survival difference but looking at the first few months, there were actually several patients that progressed very rapidly on ipilimumab and nivolumab, and never managed to switch to dabrafenib and trametinib and unfortunately died relatively quickly. We have different paces of the disease that we take into account and care about. We care about brain metastases. A very important treatment decision can be relatively easily made in the presence of brain metastases, which I know we will address a little later. We look at the extent of the disease, as in how many tumor sites are involved. Do you have lung only or do you have lung and liver lymph nodes, bone metastases. Basically, the more organs that are involved as you would expect, the more the prognosis kind of worsens. That's independent of a tumor burden because tumor burden is also kind of how large each of those lesions are but tumor burden is one more factor we think about. Finally, as I mentioned before LDH being high or low or normal or if it's actually higher than the two times the upper limit of normal. Those are important parameters that I look at for every patient that I see. Obviously, not to underestimate the fact that any of our treatment options also will induce toxicity in those patients. I also care very much about the patient's comorbidities, performance status, any sort of prior exposures to treatment that can guide my treatment decisions or any previous history of toxicity with anti-cancer treatment as well.

For this particular patient, our 47-year-old with a singular lesion in her lung and the absence of brain metastases, she does have a BRAF mutation and she has a somewhat elevated LDH. This is a patient that I consider immunotherapy first, no question about that. Again, as we have just discussed, the fact that we have a survival benefit to starting immunotherapy first. In her case, I think either combination of ipilimumab and nivolumab or nivolumab and relatlimab would make sense. As we discussed briefly, we usually think about ipilimumab and nivolumab as the combination we use for our highest-risk patients. You're inducing a toxicity rate of close to 55% to 59% with those patients. If you feel that there's very important to control their disease, then you can kind of justify that much toxicity. However, RELATIVITY-047 also showed that nivolumab and relatlimab is highly active in patients with high LDH even with increased tumor burden. In this case, if you can treat her with a combination that would give her good benefit and has a lower rate of toxicity of about 21%, I would personally favor using that combination but it's a very appropriate discussion to have with the patient. As in, you have two different combinations available. One of them seems to carry a higher response rate. We don't know that the ipilimumab and nivolumab combination doesn't seem to have a better PFS or a better OS at this point yet. The only difference that we can point to in terms of efficacy is a response rate difference where it's 55% for IPI and NIVO and maybe closer to 45% with NIVO and RELA. It's a discussion I would have with that patient. My personal recommendation because it's a singular lung lesion and the only poor prognostic factor is the LDH, I would actually consider treating her with nivolumab and relatlimab as a first line.

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