Stage four melanoma treatment options and how we got here – ippilimumab and vemurafenib explained

We have had so much that has happened in the past few weeks and my body and brain have just been so exhausted at the same time, that I have gotten woefully behind on my blog updating. While I have for the most part used this blog as my own way of processing and working through many of the spiritual aspects of our journey, Kevin and I both feel that this blog needs to serve another purpose as well. We feel a strong desire to give back to the interwebs and to other melanoma patients as well. We have found a wealth of information and resources online, and many of them have come from the blogs of other melanoma warriors. I have often found this information infinitely more helpful than the academic journal articles that I have slogged through to try to understand the various treatment options out there. Regular people usually write like, well, regular people. With that in mind, Kevin and I have decided that we want to share in as much detail as possible the medical side of our journey, primarily for the benefit of those who go after us. We haven't always given tons of information, because we know that treatment choices tend to be personal and often controversial. It's hard to tell the world we are going to do “X”, knowing that some folks will feel very strongly we should do “Y” or “Z”. But that said, we feel it is important to try to share EVERYthing we've been learning in as much “regular people talk” as possible. So if you find posts like this boring, feel free to skip over, knowing that I'll put the words “Kevin update” in the title if there is real news regarding his health and plans. This post is the first of many to be dedicated to all the folks like us who are frantically scouring the internet, getting a crash course in medical terminology, and wondering how their liberal arts history degree is ever going to help them navigate a VERY complicated world of VERY complicated melanoma treatment options.

On Thursday morning, Kevin had an appointment at the National Cancer Institute at the National Institutes of Health in Bethesda, Maryland. We found out about the NIH and the clinical trials (they call them protocols) that are offered there through another melanoma warrior named Jake Richter. Sadly, Jake’s battle took a difficult turn, and he passed away in June. I never met or even corresponded with Jake, but his extremely thorough blog posts were invaluable to me, as they were chock full of useful data. We will be forever in his debt.

I’m not sure I’ve explained very well how we ended up on this crazy adventure to the NIH and then on to UCLA, so first a little back story. I know I posted the day we received the results of Kevin’s scans that showed that the IL-2 had not had enough impact to warrant continuing treatment. That was on Wednesday, August 22. Our doctors made an appointment for us to meet with them on Monday, the 27th, so that they could have a little time to research our options and discuss them with the other members of our team (one of the benefits of being at Emory is that there is a multi-disciplinary approach and tight coordination between our surgical oncologist, radiation oncologist, and medical oncologist. There is also a tumor board that meets regularly to discuss the more “interesting” cases of which, unfortunately, Kevin is one.) When we met on Monday, we were unfortunately told that Emory did not have any clinical trials for stage four melanoma that were open at this time. The options that Dr. Lawson discussed with us that Emory could provide were the two new FDA approved treatments for stage four melanoma, ipplimumab and vemurafenib. These two drugs were both approved in the last year, and as they are so new, there are continuing trials looking at their efficacy in combination with other potential treatments.

Ippilimumab is a form of immunotherapy (the interferon and the interleukin-2 treatments that Kevin had already had are also forms of immunotherapy). As I’ve mentioned before, the main premise behind immunotherapy is getting to help the body’s own immune system attack the cancer cells. This has proved an especially important path to explore in melanoma treatment, as melanoma is very UNresponsive to any forms of traditional chemotherapy and seems very tightly connected to immune responses. Ippi works differently than the two older forms of immunotherapy, interferon and IL-2. In both of those cases, the patient is infused with man-made versions of interferons or interleukins, which both occur naturally in the body. If I’m correct, the main premise is simply to give the body more of these proteins to better be able to fight off the cancer.

Ippi (also known by its brand name Yervoy) works differently in that it is what is called a human monoclonal antibody. Basically, what ippi does is it keeps our immune system turned “on.” We have a natural mechanism in our body to turn our immune system “off” when we’re no longer sick, and since cancer cells are tricky little buggers, they try to convince our immune system that they are not “sick” cells and thus an immune response is not necessary. So if ippi can then block the mechanism that tells our immune system to turn “off”, our body’s natural immune response can have a better chance at continuing to attack and kill the cancer cells.

Ippi works really well in comparison to IL-2 or interferon. It’s a huge breakthrough in the melanoma field, especially considering there were no new drugs to be FDA approved for advanced melanoma in nearly two decades. But still, the response rates haven’t been great (data suggests between 10 and 20 percent) and while the responses appear to be durable (long lasting) there are some very significant possible side effects. The biggest concerning side effects appear to be GI issues, like colitis and very severe diarrhea. With close supervision and good communication between patient and doctor, these side effects can be mitigated, but often a patient ends up in the hospital or has to decrease or stop treatment. All for only a little bit better chance of success than IL-2. Add to that that Ippi is a slow acting treatment. The regimen is one infusion every three weeks for four cycles. Scans would only be done at the completion of treatment, and even then they might not show a response, thus requiring another round of scans a month later. So basically, it would take 3-4 months to show if there was any response to ippi at all (with only a 10-20 percent chance that there would be).

Our Emory team also told us that we could consider Vemurafenib. This is the other new drug for treatment of stage four melanoma. It works in a different way than immunotherapy. It falls under a class of drugs called targeted gene therapy. It only works in patients who have a mutation called BRAF, of which about fifty percent of melanoma patients have. Kevin and I were happy to find out that he has the BRAF mutation, as this means that vemurafenib is always an option. (also called Zelboraf) has had GREAT success, and very very high response rates. The photos I’ve seen of before and after scans are just stunning. Essentially, vemurafenib is a BRAF inhibitor, and immediately puts the brakes on continued growth of melanoma cells by interrupting this BRAF pathway. We were initially very excited about vemurafenib (as was the whole melanoma research community) because the response rates were so high. In fact, the responses were so good that during randomized phase three trials, an ethical dilemma was created by placing anyone on the control arm of dacarbazine, a chemotherapy drug known to have ridiculously low response rates for melanoma, but at the time was considered the “standard of care” against which vemurafenib needed to be tested. Literally the vemurafenib arm was experiencing greater than 80 percent partial to complete regression and the dacarbazine arm has less than 5 percent response rates. They actually ended the trial early because it had become unethical to leave folks on the control arm knowing that vem worked so well. There’s a great pulitzer prize winning article series in the New York Times chronicling the development of this drug.

So, if the drug is so great, what’s the catch? Well, even though it was working so wonderfully, and invoking what some called the “Lazarus effect”, literally healing patients from their deathbeds, the effects were not long lasting. After about 6-18 months of great quality of life and near total tumor regression, most of the patients saw their cancers come back in full force and then died rather quickly. This is not for nothing, as it is still substantial progress in the field of advanced melanoma treatment, but we pretty much decided that we’d like to keep vemurafenib in our back pocket, to be used only after we’d exhausted other, curative options or if his cancer appeared to be suddenly growing very quickly and we needed immediate results.

We of course would love to see immediate results right away, but are realizing that it is more important to be patient with a slower acting drug like ippi or something else than to jump to vemurafenib knowing that for most patients vem only buys them time. We are still hoping to buy Kevin 15 years or more, not just 15 months.

So, after going over the few options that Emory had for us, we realized that it would probably be wise to seriously research some of the many options that are currently in clinical trials. This is yet another time that I am realizing that it is SO important to be your own best advocate (or your spouse’s best advocate). As much as I try to stay off the google in general, I had been following the state of melanoma research these past several months, knowing that new developments were coming up all the time. Amazingly, we are currently in a bit of a renaissance of melanoma advances, as there had been such a huge dry spell up until about 18 months ago. We sense that researchers are SO close to finding something that could transform advanced melanoma from a near certain death sentence to a chronic condition or even better a completely curable cancer.

This truth is no more evident to us than in the story of our friend George. In 2005, just a few months before Kevin and I got married, one of Kevin’s best friends, who he’s known since childhood, was diagnosed with leukemia. George found out that he had a form of leukemia called CML, which a quick google search on his part told him he’d pretty much be dead in five years. There was basically no other option than a bone marrow transplant which is risky and doesn’t have great numbers for success in the case of his type of cancer. A new drug was in trials called Gleevec. It had literally come onto the scene just months before. This drug is also a type of targeted gene therapy like Vemurafenib.

Once George got started on this drug, his cancer slowly moved to complete remission. He continues to take the medicine to this day, and it is basically his own personal miracle cure. No one knows if someday his cancer will develop an alternate pathway and return in full force the way that melanoma tends to do with vemurafenib. But for now, folks with CML have not been recurring and the drug continues to work amazingly well. It has truly turned CML from the worst kind of leukemia to get into the best kind.

George’s experiences are another reason we decided to look with hope to the clinical trial world. So that afternoon, after our discouraging appointment at Emory, we sat in a coffee shop and opened up our laptops. I remembered Jake’s blog posts about his experiences at the NIH in Washington D.C., so decided to start by looking there. The next part of the story will have to wait until tomorrow, as I believe I detect tiny voices through the baby monitor, and snuggling with my little ones will have to take precedence for the rest of the day.

Love to you all and thank you again for ALL of your continued support, prayers, encouragement, and love. It means so much to know how lifted up we are.

-Rachel and Kevin

7 thoughts on “Stage four melanoma treatment options and how we got here – ippilimumab and vemurafenib explained

  1. Hi Rachel: Sounds like Hope has led you from wondering to research and God has lifted you up once again. What a roller-coaster ride – up-and-down.
    May you continue to “go with the flow” – (what a trite example – I am sure you can think of another one). Good to hear your little ones are back with you on this journey.
    Love, Irene

  2. Rachel,
    Thank you for the update. I can not wait to hear the rest if the story.
    I miss you friend. I am glad you are in the midst of home and people that are loving on you… And your kids!!!

    Still praying that there is something out there that will bring healing and kill those dang cancer cells!
    Give Jude and Evie a hug from Auntie Candace- the stranger they have never met, but who will love on them when we get to meet face to face!
    Love you sister.

  3. When He created that is. I don’t remember her ever being crated. Anyway, man should not be alone, he needs help like you give Kevin.

  4. Rachel, i read what you wrote & ir sounds like you have a few opitions. I was just wondering what happen when u went to UCLA. Andrew & i prayed for you this morning. Your in our much daily continued prayers. We both love you & hope to see u again soon. God bless you.


  5. Rachel i am following your blog and praying daily for your family. I have a very positive feeling that you guys are goona be successful in your fight. I have read a bit of the blog “WilliamFightingCancer” who has wonderfully gone into remission with a combination therapy clinical trial. Is this an option for kevin?

  6. Hi Rachel – it’s me again…
    I just read (re-read) your blog for the third time – the research area of my brain has been sleeping for a couple of years – you woke it up and I thank you. I am amazed at the work being done in the area of melanoma and I wonder how John McCain (of hot sun Arizona) has survived all these years – maybe it’s his nasty
    Keep your blogs coming – my brain needs the exercise.

    Love you and Kevin,

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