Seeking advice for metastatic melanoma treatments

I am new to the forum and here representing my wife, Sara, who was diagnosed with stage IV melanoma this past April and is currently reaching the next stage of treatment options. Just hoping for any advice, words of wisdom, similar stories, hope, etc. I’ll do my best to summarize her situation here, but it’s been quite an unusual rollercoaster and this may get lengthy. FYI she is 38 years old, mother of two (ages 8 and 6), and a contract attorney director for a large healthcare company. We live in Maryland, about 30 minutes outside of Baltimore.

The first sign of something being off was this past winter, starting in Jan/Feb, when her left tonsil appeared to have an infection of some sort. Week-by-week, things worsened as she visited various doctors and all the antibiotics she tried, gradually increasing in intensity, failed to completely get rid of the weird mass growing on her tonsil. Eventually, the ENT she started seeing recommended removing the tonsil, and that was done on April 18th. A week later, analysis of the tonsil tissue revealed that it was malignant, and the ENT ordered a CT scan for the following morning, on the 26th. The results came back by the early afternoon that there were signs of bleeding in her brain and that she should get to the ER at the University of Maryland Medical Center as soon as possible.

Within a few hours of being at UMMC, she had addtional CT and MRI scans conducted (and eventually a PET). There were 2 larger tumors in her brain, one on each side, that were bleeding, along with 3-4 very small lesions that I suppose were so insignificant for doctors to really mention them much. She also had a larger mass near one ovary, and two very small nodules in the lungs were noted, but doctors did not seem concerned given how small they were – could be nothing, they said. She also pointed out two spots on her scalp that had been there for maybe 10 years or so. From her best recollection at her early 2023 dermatology appointment, she remembered the dermatologist saying that they could be removed if they were bothering her, but did not otherwise look concerning. She had noted how they would occasionally bleed when she hit them with a comb, so that was annoying, but I guess the dermatologist did not find anything concerning with them and left them alone (kind of unusual given my experiences, where they seem ready to remove even slightly suspicious spots right on the spot). I honestly can’t remember what these spots used to look like, but at this point the one is definitely large and raised up enough to be very alarming, though it has also been biopsied and may have changed appearance a bit after that procedure.

Being admitted to the hospital on a Friday was not ideal, and I think it wasn’t until Monday when the PET scan was done, but we were sent to the neuro ICU, and gradually doctors from various specialties came to visit and lay out a gameplan. The first priority was brain surgery to remove the larger tumor (4-5 cm) on the right side of the brain, and this was done on May 3rd, with everything going very well. We went home after 11 long days in the hospital on May 6th.

The next stage of treatment was 6 fractions of radiation for the remaining lesions in the brain, as well as the surgical site, and that began on May 20th and concluded on June 5th.

At some point during all of this the NGS advanced sequencing revealed that all tissue samples – from the tonsil, the brain, and the scalp lesion that was biopsied – were cutaneous melanoma and BRAF mutated.

While all of these treatments were occurring, we were also meeting with Dr. Petr Hausner, melanoma oncologist at UMMC, and discussing a plan to begin immunotherapy (Opdualag) once radiation had concluded and she had tapered off of the steroid (Dexamethasone). He wanted a much shorter taper off of the steroid than the rad-onc doctor wanted, which we tried but my wife quickly began having symptoms of pressure in her brain, headaches, and even a little bit of flashes in her eye, so we went back to the original taper plan after a few days off. Dr. H did not seem concerned about this, citing my wife’s very low tumor burden and otherwise healthy situation. I should also mention that by this time she had seen a gyno-oncologist and it appears that the mass near her ovary is not “lighting up” on scans as anything cancerous, and may be a benign cyst. Either way, we are planning to have it removed whenever possible (we are done having kids), and that way we will know for sure.

Either way, Dr. H did not seem in a rush to begin immunotherapy at that point and was okay with the slower steroid taper. The bulk of my wife’s tumor burden really seemed to be the tonsil (removed) and the brain (removed/radiated), and he also wanted to leave the scalp lesion on in order to have an external indicator of how she responds to the immunotherapy. She had another round of CT scans done on June 26th and things appeared stable.

Her last dose of the steroid was July 7th, and we were scheduled to have her first infusion this past Thursday, July 11th. Unfortunately, things did not go as planned. After coming off the steroid, and even a little bit in the week prior when she dropped from 2mg a day to 1mg, her headaches had increased throughout the day. Towards the end of the day on July 10th, she also started having a few issues remembering words, pronouncing things, and making little mistakes when texting. These language issues worsened on the 11th and were becoming very concerning for me, though it would come and go sometimes. We met with Dr. H after her initial bloodwork and described her symptoms and he ordered a CT scan and then later an MRI to get better detail of what the situation in her brain is. A rad-onc doctor also reached out to assist in explaining things. The right side that was operated on looks great, but the other large tumor on the left side has a fair amount of edema and some bleeding (which I believe he said was the original bleeding treated by radiation). This tumor has grown slightly since an MRI that was done on May 5th, but also keep in mind that radiation did not begin until May 20th, and we were told that the effects of radiation often take many weeks to really take place, and that some growing can happen before the tumor actually shrinks following radiation.

Both doctors agreed that she should go back on the steroid immediately in order to get the edema under control. It was also causing a slight midline shift. She did a loading dose of 10mg that evening and is now doing 2 doses of 8mg each until all symptoms go away. Symptoms are much better at this point (typing this on July 13th), with only mild pain (i.e. when standing up) and very subtle and harder-to-notice issues with speech. How long she will be back on the steroid depends on how long it takes for her symptoms to completely subside, but I would imagine about another 2-3 weeks.

At this point, Dr. H has recommended that we go with the standard of care approach and switch from the initial plan of Opdualag immunotherapy and try the targeted therapy tablets (I believe it’s the combo of Braftov and Mertov?). We are meeting again with him next Thursday (July 18th), by which point the tablets should be ready.

Based upon our conversations, my understanding is that these tablets are very effective in preventing the spread of melanoma and can even shrink tumors in the brain and body, but that it only provides a long-term effect for about 10% of patients, and that the cancer cells can figure out a work-around in about 6-7 months, at which point another treatment type will be needed.

He also said that the immunotherapy treatments have not been found to be as effective when done following the tablets, but this was somewhat unclear. I was also confused as to why he would not want to just wait maybe another 2-3 weeks until she could taper back off the steroid to hopefully start the original immunotherapy type then. I understand there’s no guarantee that she’d be able to taper off successfully, and that the steroid interferes with the immunotherapy treatment so they cannot be done simultaneously, but given her relatively low tumor burden that he referenced before when she first had to do the longer taper, why is it problematic now?

One other option – an “experimental” one that he mentioned – was the immunotherapy combo usually used for liver cancers – Atezolizumab and Bevacizumab, the latter of which could take the place of the steroid in decreasing swelling/edema in the brain. It doesn’t seem like he thought this was the best option to try, but I was kind of confused as to why the Bevacizumab could not be incorporated into the originally planned Opdualag.

I suppose the biggest upside of starting the tablets is that we’ll be able to get the next treatment stage started within the next week, can continue the steroid to help with the brain edema as needed, and can also proceed in the near future with the ovary surgery (not possible with the experimental option because Bev. can cause blot clots). One downside Dr. H did mention was radiation recall, but he said we should be far enough away from the radiation window by now that the likelihood would be very small.

This seems like a really pivotal juncture, and honestly the feelings we’re having coming out of this recent visit are nowhere near as optimistic as the previous one when we planned the first infusion, hearing things like “very low tumor burden” and “cure” (a decent possibility with the immunotherapy) repeated a few times, and shared smiles with Dr. H and his nurse. We did also reach out to John’s Hopkins and are going to meet with Dr. William Sharfman this Wednesday, a day before we meet with Dr. H again.

I haven’t done a lot of thorough research up to this point, but have looked through the outline of resources put together by the Chaotically Precise blogger, which were incredibly helpful, though a bit scary given that none of the doctors have explicitly discussed things like survival rates with us yet. Any advice, wisdom, stories, and/or positive vibes that you can send our way would be much appreciated. Thanks just for taking the time to read it you made it through!

Brian (Sara’s husband)