- December 11, 2020 at 3:18 pm
I progressed to S4 in Jan 2o with mets in spleen, neck and stomach. I had failed Optivo in a 2017-18 CT.
I got 2 treatments of the ipi/optivo combo after progression, then 2+ months colitis which the Onc now says “nearly killed me”. Had 6 weeks in hospital in total.
The scan after discontinuation of treatment showed no cancer. (June)
The scan after that showed possible activity in spleen again (Sept).
Ordered for 2 month follow up, my late November scan shows no activity in the spleen, but “too numerous to count” micro-lesions (my description) that look like “bird shot” or a “star chart overlay” on my PET scan. I can see numerous little specs growing where skin is white/translucent (like upper leg).
My Onc has discussed the options in overview; step one is finally getting braf status. If that is open, it will be an easy next choice. If not, well, I will ask that separately, it’s a bigger question. Including whether Ipi will ever be on the menu again.
My inquiry today is more generally of any familiarity with any discussion of this type of fact pattern; where you get response, but then a “measles like outbreak” of melanoma activity all over the body.
I know this doesn’t generally bode well for me, but not sure where to start looking as to this stop/start growth pattern as it relates to ongoing treatment and status. I am considered a “responder” according to MD. He is a top guy, and is genuinely surprised at these developments, but didn’t have a lot to offer on similar situations, or the issue of combo response, which then fails..
I know a few others here are in my boat, or I now in theirs.
Bonus question if you know, what are the limits of using T-VEC injections when you would have 100 or so subcutaneous legions.?
Thank you as always, links and buzz words appreciated.
DAMN! Melanoma DOES suck great big green hairy stinky wizard balls, doesn’t it? I have known of others with this response. I will cross fingers and toes that your lesions are BRAF positive. Meantime and in conjunction with – I would certainly pursue intralesional therapy!!! No, you wouldn’t inject EVERY lesion. Nor should you have to!!! No matter the poison picked, all have shown responses in the injected lesions as well as “by-stander” lesions that were not injected. I mean – what the heck! I would go for it.
- December 11, 2020 at 4:28 pm
Here are posts I have on the subject: https://chaoticallypreciselifeloveandmelanoma.blogspot.com/search?q=intralesional&max-results=20&by-date=true
There is also this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066689/
Hope that helps at least on the intratumoral/intralesional front. Hang tough. Yours, celeste
- December 11, 2020 at 6:18 pm
I am not aware of anyone posting with symptoms of a measles like outbreak – am sorry for this but also am hoping that this is not melanoma. Are you sure that it is, because I have not read about it here. (Sorry)
Agree on need to check BRAF status. On TVEC, I took it in conjunction with pembro as neoadjuvant and the two together removed my tumour (where pembro alone had not been sufficient – pembro removed a 0.7cm tumour but not a larger one). I am not sure how good it would be at multiple tumours, but since yours all seem small then it could work. I like the logic of the treatment and it might work – it seems you did or do respond, so tvec might give the pembro an extra kick. As celeste says, you dont have to inject all the lesions. It just gives a kick start to the immune system. I liked the review article Celeste posted and do wonder whether TVEC plus pembro or nivo should be the first line of defence for stage III non resectable. The side effects were a terrible fever (worst I have experienced but nothing like covid fever reports) for maybe 3-4 injections, but this probably means the TVEC is working or doing something so its worth suffering.
I hope for better news for you soon
Best wishes Mark
MelMelParticipantI think the following article will explain the mixed response you are experiencing. Unfortunately, I was unable to copy the figures however you can clearly see them when you go to the posted link on the bottom of my post. Here is the abstract and Figure 6 explaination for the mixed response melanoma patient following immumotherapy. One can clearly see how tumors respond differently to identical therapy and why various different therapies are required to combat melanoma.
- December 13, 2020 at 3:56 am
Tumours can escape T-cell responses by losing major histocompatibility complex (MHC)/ human leucocyte antigen (HLA) class I molecules. In the early stages of cancer development, primary tumours are composed of homogeneous HLA class I-positive cancer cells. Subsequently, infiltration of the tumour by T cells generates a vast diversity of tumour clones with different MHC class I expressions. A Darwinian type of T-cell-mediated immune selection results in a tumour composed solely of MHC class I-negative cells. Metastatic colonization is a highly complex phenomenon in which T lymphocytes and natural killer cells play a major role. We have obtained evidence that the MHC class I phenotype of metastatic colonies can be highly diverse and is not necessarily the same as that of the primary tumour. The molecular mechanisms responsible for MHC/HLA class I alterations are an important determinant of the clinical response to cancer immunotherapy. Hence, immunotherapy can successfully up-regulate MHC/HLA class I expression if the alteration is reversible (‘soft’), leading to T-cell-mediated tumour regression. In contrast, it cannot recover this expression if the alteration is irreversible (‘hard’), when tumour cells escape T-cell-mediated destruction with subsequent cancer progression. This review summarizes clinical and experimental data on the complexity of immune escape mechanisms used by tumour cells to avoid T and natural killer cell responses. We also provide in-depth analysis of the nature of MHC/HLA class I changes during metastatic colonization and contribute evidence of the enormous diversity of MHC/HLA class I phenotypes that can be produced by tumour cells during this process.
Keywords: CD8 cell; antigen presentation/processing; cancer; cytotoxicity; immunotherapy.
If you look at Figure 6 it shows the results of a mixed responder melanoma patient to immunotherapy with the following explaination
Figure 6 Different human leucocyte antigen (HLA) class I expression in metastases from the same patient. This figure shows two metastatic lesions analysed in a ‘mixed responder’ to immunotherapy (a). One lesion is capable of up‐regulating HLA class I to induce a T‐cell response and regresses. The other lesion cannot up‐regulate HLA class I and eventually progresses. The type of molecular alteration (hard or soft) responsible for the HLA class I down‐regulation plays a pivotal role in these different responses.
Here is the full link with pictures! This concept is interesting but I would stick with melanoma experts and two references used by this author are by melanoma expert, so I will add them as well..https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856929/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007206/
- December 13, 2020 at 8:40 pm
Dirk Schadendorf from Essen Germany is part of many of the ESMO melanoma peer panels on Onclive and is one of the authors of the following paper which was one of the references in MelMel paper.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460020/
- December 13, 2020 at 8:44 pm
Huge thanks for the replies and links! Greatly advanced my understanding.
- December 15, 2020 at 8:24 pm
Sometimes you just don’t want to re-invent the research wheel!
The word “interferon” (in combination, etc.) came up from the MD and I did not understand why it would . I am starting to see why it might (IFNy resistance?)
I will say parenthetically that I found it impossible to sign on to ebullience after a clear scan. So with no big highs you are rewarded with no low lows. (After 3+ years.)
I am very grateful to all who have shared their most difficult moments. I am very inspired by the fierce fighters amongst us as I rejoin the battle!
Still debating whether I will make it a personal mission to help Bubbles find a new Melanoma metaphor. (j/k, LOL)
Bring it!!! I am more than open to a metaphor adjustment!!!!! My long used phrase is a combo of what my son (aged 12 – 20 at the time) – “Well, that sucks balls!” – and sister – something that involved stinky green wizards – would reply when I would give them updates on my status – which for a while there – was in fact, pretty sucky!!! Would be happy to go into 2021 with no use for any such phrase – but a new one on tap, should we need it, might be just the thing.
- December 15, 2020 at 10:50 pm
Hang tough. Sorry you have to rev up again, but I know you can. Don’t know that I can provide any great answers – but shout out questions, ideas, complaints – as you have the need. Yours, c
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