Questions about Stage 4 treatment options

So the data for one treatment of Ipi+ Nivo then stopping for grade 3/4 IRAE (immune related adverse event) is the same if you had not stopped or at least pretty close based on long term stats from early combination trials with Ipi+nivo. new stuff popping up happens and you can be treated with targeted therapy or in some cases targeted radiation, Univ of Chicago has done a lot of research in this area of combining radiation. one of the big names in melanoma (Dr Jason Luke) went from Harvard to Chicago to study under Dr. Tom Gajewski (see following link).He is now at University of Pittsburg running lab developing new melanoma(solid tumor)drugs in immunotherapy area. mD Anderson has a few stars, I like Dr. Michael Davies and Dr. Hussein Twabi if you decide to get second opinion. every big research center will have new areas of research and various clinical trials from different drug companies. It can get overwhelming trying to figure out best option. lAG-3 + nivo is about to be approved, and would be an option down the road, TIL’s from LN-144 trial of Iovance Lifileucel should be not to far from approval as well based on great responses in clinical trials. https://news.uchicago.edu/profile/thomas-gajewski

Sorry for all that you and your wife have endured and are facing. Here are some thoughts and posts (yes, there are articles in the posts – because I think it is important to give real live data from Melanoma Big Dogs – so that it is clear that I am not pulling info out of the air or even my own head – but there is also my break down of the report that folks usually find to be helpful in making them understandable) that may interest you ~

1. Though I think at this point you have learned these basics, there may be some info that clarifies in this primer of current melanoma care I put together here – primer

2. I gave you a link to many posts about neo-adjuvant treatment in a prior thread.

3. In regard to colitis after immunotherapy – this may give you some hope: Side effects to immunotherapy – Part 11! – Oh MY!!! BUT!!! Colitis may be associated with a favorable response!!!!

4. While there are occasional reports that intimate steroids may put a damper on response to melanoma therapies – the vast majority of them demonstrate that folks required to take steroids due to side effects or pre-existing conditions DO attain a positive response to their therapy that is comparable to everyone else!!! Put ‘steroids’ in the search bubble of my blog if you are interested in a zillion articles. Many folks are still here on this forum BECAUSE steroids allowed them to continue or resume their treatment after problematic side effects were brought under control.

5. As to – Do folks who have to stop the ipi/nivo combo gain a response should they take it (or other immunotherapies) again later? The short answer to that is yes, they can. Sometimes the data demonstrates the response rate is not as high as when the patient is treatment naive, but it is still possible. There are many patients on this forum who are still here due to repeated rounds of immunotherapy after a prior round earlier in their history.

6. In that same vein – It is important to recognize that ipi (Yervoy) is the bad boy of side effects in immunotherapy. Either of the anti-PD-1 products (pembrolizumab/Keytruda or nivolumab/Opdivo) despite a list of possible side effects that are similar to those caused by ipi, they are generally much better tolerated with a decreased incidence of those side effects. To that end, it is certainly worth considering the possibility of taking nivo alone at some point, should your wife need it. As a melanoma patient – 3b in 2003, advancing to Stage IV with brain and lung mets in 2010 – I am still here due to radiation to the brain mets, surgery to other body parts and participation in a phase I clinical trial of nivo as a single agent from 2010 to 2013. My last dose of nivo was in June of 2013 and I remain NED for melanoma today. So – there is hope. (Also – regarding radiation – as you will note in the primer – radiation alone is not very effective in melanoma. However, when it is COMBINED with systemic therapy – it can provide a real boost to response. Radiation can be used in the body or the brain, so that is another thing you might talk to your onc about.)

7. If targeted therapy, or the other things I have mentioned do not work out – your wife would still be a candidate for TIL or a clinical trial. Clinical trials are a whole thing unto themselves – but they have saved many of us. It is true that the more treatments you have had, the more complicated meeting entrance criteria can be, but they are there.

8. As Edster touched on – some new melanoma treatments are soon to be available and seem very promising. Here are a couple of posts about anti-LAG-3 – relatlimab with nivo. It boosts the response to nivo with fewer side effects than when nivo is combined with ipi – Anti-LAG 3

9. Another promising drug is NKTR-214 – Bempeg. Here are some reports: Bempeg

10. Finally, I don’t give you all this to overwhelm – rather it is to give you hope. Your wife still has current FDA approved options. (The targeted therapy she has started, radiation, and/or nivo as a single agent just as a start.) Further, there are many viable treatments on the horizon as well as TIL and clinical trial options. Knowledge is power. Doing the research and learning the new language that is melanoma is a huge way you can support your wife and get her the treatment she needs. You are lucky to be in an area of the country with good melanoma treatment. However, a second opinion is never a bad thing should you think you need it.

Ask more questions as you have the need. There are many smart, knowledgeable and caring people on this board. I wish you and your wife my best. Celeste

HELLO MAX! I am new to these forums, and I just posted a long, long post about my father’s five year journey with Melanoma. (Sadly, we lost him in October of 2021). We – like you – were with the University of Chicago. (We were with Dr. Rampurwala – out of the Orland Park, Illinois facility). I had often thought about reaching out to the guru at UOC – Dr. Gajewski – but I never had – and I would THINK that being a University Hospital – that they were all in discussions about the cases etc.)

I hope and pray that your wife can beat this! I know your fears, I know your struggles – but one day at a time, and one treatment option at a time and living every day like its the last is the best advice I can give.

When you note that your wife seems 100% fine – that is exactly it! If no one told you or her that she was “sick” you wouldn’t believe it! That is how it was with my father! You would never ever know that there was this beast inside causing all this harm. Its so sad and so unbelievable.

I also wondered if it would be of any benefit to look into places like MD Anderson – or Mayo Clinic – but I honestly have (had) the utmost faith in the University of Chicago. EVERYTHING I spent HOURS researching on – the UOC and our wonderful doctor – we right there on top of. The one thing I always asked our doctor was about that Interferon- or IL-2 those immunotherapy treatments – and I guess those are super old (in today’s standards) and have super high risks and the newer immunotherapies have so much more favorable results – but at the same token – I’ve seen stories where people have made it 10+ years after having those older immunotherapies so that has always been in the back of my mind ….

I also wondered if even though my dad “failed” an immunotherapy IF we could return to it later – like just to try it again – and the answer has always been “no” from the doctor. I guess they feel that once the body has responded to it – and then stopped responding – we do NOT go back. (Although again, I’m not sure I like or accept that answer – but it is what it is ….)

My dad was able to have a response to the targeted therapy BRAF/MEK for about nine months (and this was after a first line treatment in 2018 of Keytruda, then after about 10 months and some progression we did the IPI/NIVO combo for 4 cycles and then stayed on Nivo for almost another year before progression – and that’s when we started the targeted therapy). It was after we progressed on the targeted therapy that we had no choice but to go to Chemo / Radiation.

I hope and pray your wife can beat this, Max – you will all be in my thoughts and prayers. If you don’t mind me asking – which doctor are you seeing at UOC ?

Second opinions can be valuable. There is a real disagreement among oncologist about steroid use during immunotherapy. My oncologist really thinks he is right in that steroids CAN manage side effects DURING immunotherapy. I was on a steroids while undergoing radiation and then immunotherapy and completed two years. Basically the drugs should be allowed if they allow you to stay in immunotherapy.

MasAndersonJr,

I see the experts have weighed in on your wife’s case (they are the best). I just wanted to chime in on my personal experience. I did Opdivo single immuno for 10 months for stage IIIc melanoma until it stopped working. Went to Opdivo/Yervoy for 3 cycles until it was determined it wasn’t working, so we moved to Braf/Mek, which I had issues with but it got the job done. I had surgery in June 2021, and all went well, but we failed to see I already had 8 brain mets so that was an unexpected treat in September 2021. So, after radiation/steroids I am back on Braf/Mek (lower dose) and hanging tough!

The point of my response is never to give up hope. I thought I was finished last September, but I am back to working full-time and just taking it one day at a time. I wish you both the best!
Jenn

I am new to this forum but so happy to find it, and especially this thread. Need some advice on how to proceed. My husband was diagnosed at the end of January 2022 with Stage IV Melanoma. It was found by accident. He had an xray on his stomach after having an appendectomy which shot a little high and saw a shadow on his lung, PET and biopsy confirmed a 23mm X 17mm melanoma in the lower left lobe. A brain MRI was then done which confirmed there were four small brain mets (3mm,4mm, 5mm,6mm). Combination immunotherapy with Nivo+Ipi began on Feb. 16, 2022. After the first treatment he had rash and terrible itching and some diarrhea which got worse and the dr postponed the second treatment by one week to see if it cleared up with change in diet. We were devastated that his treatment had to be postponed and maybe stopped. My husband was diligent and took Lomotil and did the BRAT diet and things got better. He had the second treatment with some diarrhea but not bad, and last week had the third. Before this third treatment, the brain MRI was repeated and showed that two of the mets were smaller and two could no longer be seen. We were so excited. However, now after this third treatment his diarrhea is much worse and at times uncontrollable even with the Lomotil and diet. He has also lost a lot of weight. In the past the dr has always asked if there is cramping, black mucus or blood in stool and that is always a no. How do you know when diarrhea is a result of colitis? He has diarrhea, sometimes urgent, lost weight and is fatigued. Is this enough to diagnose it or must there be blood or black stools, mucus and abdominal pain. Sorry for such a graphic question. Dr has prescribed steroids to have on hand in case….we have a call in to the dr right now. I saw in this thread that not completing the four treatments because of the steroids doesn’t mean it won’t work anyway, but need reassurance and also the question of whether the second part of the treatment, Nivo alone, will be able to be done if he begins the steroids. I also saw in one comment from JudiAU that the dr still did treatment along with the steroids. Any help would be so appreciated!

Thank you so much, Ed. This is very helpful. My husband has an appointment today. He doesn’t have the number of events but he isn’t eating very much. His weight before he started treatment was about 163…this morning he weighs 144. So pretty scary. His oncologist, Dr. Philip Friedlander at Mount Sinai in NY had agreed that he should take the Lomotil to control and as I said it had been helping until now. He has an appointment today and I will suggest the blood testing and a CAT scan if they don’t, per your experience. Again, appreciate the encouraging words and the information about stopping treatment.