Braftovi/Mektovi + Nivo Triplet

It occurred to me this morning that I haven’t updated this thread in a while, so I thought I should.

The first thing, and most important, is that I’m still here!

The GI bleed never came back, and the arthritis hasn’t really been an issue.  Sometimes an odd joint will be creaky (the middle finger on my right hand, for example, perhaps from overuse in 2020).

I’ve continued right along on the Braftovi & Mektovi with no breaks, and the same is true of the nivo infusions.

The new side effects have been strange, and strange has become the norm. Shortly after my GI episode cleared up, I experienced the strange phenomenon of an intense need to urinate whenever I exerted myself, even if my bladder was empty. That was another day spent in the ER, when I was told to follow up with a urologist at the end of it all.  I think it was inflammation (what else?) somewhere down there making me feel like that – it calmed down over the course of the next week and hasn’t really returned.

The vitiligo has slowed, but not stopped. My skin feels very strange – sort of extremely sensitive.  Bumping into things hurts like never before, for example. Very hard to describe.

The hair on my head is about 65% gone, including my beard.  Most of my other body hair is completely gone. Any stragglers have started turning white.

The past few weeks I’ve been very fatigued.  Most of us know what that heavy, welded to your chair fatigue feels like.

I’ve recently started having some upper GI issues.  I feel bloated a lot of the time and don’t really want to eat, but then my stomach growls and hurts (sometimes nauseous) as though its empty.  So I eat, but only eat a small amount before I feel full.  If I eat too much, I get wicked heartburn. These symptoms seem to come and go, they’re not constant.

Like all of us, my hope is that the side effects are evidence of a response, especially the skin and hair changes. Of course, it seems like any tie between the two is somewhat tenuous and I’m trying not to get my hopes up. I have scans next month that will tell the tale for better or worse, but until then I’m trying to keep the faith!

Thanks so much for the kind words.  I realized over the weekend that I never posted about my scans!

I had CT scans in November, a couple months after starting the targeted meds.  Everything had shrunk considerably or was stable.  There were some very small and questionable spots on my liver and lungs, and they hadn’t changed.  The disease in my axillary and cervical lymph nodes had shrunk considerably.

My visit on Thursday was uneventful – Dr Sznol thought upon palpation that everything seemed to be continuing to shrink, and the stubborn spots may well be scar tissue. Labs looked good, so I had another nivo infusion.

So things look good for now, and I’m trying to remain optimistic like you guys.

I had new scans on Thursday, with mostly good news.

Brain MRI is negative.

Abdominal CT: “Stable subcentimeter nonspecific hepatic hypodensities. A few prominent but not pathologically enlarged lymph nodes in the periaortic chains are unchanged. No lymphadenopathy.”

Chest CT: “Except for a left subpectoral lymph node which has enlarged, overall, decreasing metastatic lymphadenopathy. Stable small nonspecific lung nodules.” With these notes: “Some of the lymph nodes contain amorphous calcification which may be related to treatment. However, a partially necrotic left subpectoral lymph node has enlarged now measuring 1.4 cm in short axis diameter, previously 1.1 cm.”

And the neck CT, where most of the action is: “Mostly a decrease in metastatic lymphadenopathy diffusely involving bilateral cervical levels, but with increase in central necrosis of multiple lymph nodes and several residual lymph node conglomerates. Exceptions include left cervical level VB conglomerate lymphadenopathy which has increased in size, left posterior chest wall lymphadenopathy has increased in size, and attention on follow-up is recommended.”

Again, the issue of whether or not central necrosis is a good thing – is the tumor dying, or is it eating healthy tissue? I guess only time will tell. Until then, less disease = a reason to celebrate!

Thanks for following along! It’s very helpful to me to be able to identify some commonality between myself and a fellow melanoma warrior that is having some amount of success, so I hope I can provide some of that to others!

The two spots that seem to have enlarged aren’t causing my doctor any particular amount of heartburn, yet. It could be inflammation from the nivo starting to work again, or it could just be stubborn disease that isn’t responding. I guess only time will tell.

How are you feeling now that you’ve started with the ipi/nivo?

I’ll try to do a quick synopsis of how I came to be where I am. When I was diagnosed in February 2020, the disease was all on my left side, and all in my lymph nodes, though it was extensive. I Initially saw an oncologist who staged me as 3/4, because it hadn’t spread to anything but my lymph nodes, and just on the left side.  Nothing ‘distant’. Shortly after, I had a consult with Dr Sznol at Smilow/Yale and decided to get my treatment there.  He wanted to be as aggressive as possible and I agreed (people keep telling me how young and healthy I am, though it doesn’t feel like that) so he staged me at 4, I think partially to make sure there would be no issues with insurance and going right to the ipi/nivo.

At first I had a great response.  The tumors that were palpable visibly shrunk. 3 months later there wasn’t as much progress on my first set of scans as we would have hoped, I think because my response to the ipi/nivo was already waning. But we stuck it out for the 4 combo does, though, because I was tolerating it well. I did have to go on a short course of Prednisone for some pretty bad joint pain that had me just about crippled, but that was it.  After the 4, we started talking about trials, and he thought I would be a good candidate for an intratumoral trial. They would inject a few of the palpable tumors and I would stay on an anti PD-1, I think it was pembro for this trial. However, it had been closed to enrollment due to Covid. So we stuck out the monthly nivo only infusions while waiting for the trial to open. During that time, it became obvious that I was no longer responding, most likely because of my high tumor burden. So they pushed quite hard to get me into the trial, and had the paperwork ready on the day of my visit at the end of August. However, when I showed up, the visible disease progression around my neck sorta knocked his socks off. The change from my last visit in July to August was drastic. He left the decision up to me, but it was his opinion that I didn’t really have time to wait and see if this trial drug would have any effect on me. The tumors had already started to push on my esophagus and swallowing certain things required some concentration and lots of chewing. A recent scan noted that the disease was occluding my carotid on the left side. He thought I’d be better served by starting the targeted therapy and getting the progression under control. We discussed continuing the nivo in combination with the targeted meds – the ipi/nivo has been described as potentially curative, while the targeted meds generally are not, so it was important to me, maybe psychologically more than anything, that I stay on the meds the could potentially cure me, and that I wasn’t just jumping to a short term band aid.

I just want to take a minute to say for anyone reading this in the future, the targeted meds are not always short term.  There are lots of examples of people being on them, effectively, long term. So don’t be discouraged!

Dr Sznol’s further opinion was that if we could get the tumor burden reduced, I may respond again to the anti PD-1. So we elected to go with all three, again, because I had been tolerating the ipi/nivo so well. The targeted meds were as advertised and dramatically reduced the size of everything in short order (I noticed a difference inside of a week, when I was able to turn my head without having to turn my whole torso). There have also been encouraging signs that perhaps I am having another response to the anti PD-1. I’ve had persistent vitiligo on my forearms and a couple other spots, and whats left of my mustache has turned white, and that seems to be traveling south to my beard as well.

The two scans I’ve had since I started the targeted meds proved out what we could see and feel, that everything is shrinking.  Well, most things.  Two spots (that I can feel, of course) have gotten slightly larger for some reason, while the rest continue to shrink. So, most things are trending in the right direction.

I’ll be honest, the side effects have been much more noticeable since I started the triplet.  My joints don’t necessarily ache constantly, but I’m not nearly as flexible as I used to be. I feel like a creaky old man! My skin is also very sensitive, I’m not sure how else to describe it. If I bump my leg on the corner of the bed I brace myself for how much its going to hurt. The fatigue is much harder to fight through. Recently I’ve been dealing with digestive/upper GI issues. Bad heartburn, feelings of indigestion. I take a Zofran if I feel like I need it for nausea, and I take a PPI every day for the acid. Really though, these things hardly move the needle as far as adverse events go, all my labs have been perfect (again with being so healthy, if it wasn’t for this darn cancer!) so we continue on and try not to complain too loudly about feeling lousy!

Thanks for the kind words! It’s always encouraging to hear good things about Dr Sznol! It always makes me smile when I’m Dr Googling something and come across him as a trusted voice in the community, speaking about the latest and greatest thing.

I’m very happy that he’s taken such good care of you! My aunt is also under his care – he shepherded her through her Interferon treatment all those years ago which eradicated her stage 4 melanoma.

I went for a consult with an ENT surgeon when the tumors in my neck were blowing up and they wanted to evaluate my swallowing, and I had a conversation with a nurse about my treatment so far. I mentioned that I was being treated by him and her eyes lit up and she said,”He’s like world renowned! You’ll be fine.”

Enough gushing – suffice it to say that I highly recommend him and the rest of the Smilow team. They’ve been fantastic. They even let me skate on parking once, when I forgot my wallet!

My insurance (United) did cover it, though without saying so, it seemed like there were some behind the scenes things that went on between the hospital and the insurance company, I don’t think there was ever even a question that it was going to be covered.

However, at the beginning of this, the first oncologist I saw sent tissue from my biopsied tumor to Foundation One for the BRAF testing, which United declined to pay for, even after appealing, and even after I started taking the medication that I could only take if I knew my BRAF status.

Dealing with insurance is unfortunately a whole other ugly side of this. Sometimes I think that the institution who’s care you’re under might make a difference – the larger cancer centers might have more muscle to flex in this area with the insurance companies. Or maybe not! It’s frustrating and maddening.