7 ms·

I work in oncology and with some of the people interviewed in the article. I want to emphasize just how exciting this stuff is and how wild it is to have patien

I work in oncology and with some of the people interviewed in the article. I want to emphasize just how exciting this stuff is and how wild it is to have patients who have a belly full of innumerable metastases, for whom 5-10 years ago we'd quote a few months' survival at best, and now on these new fancy drugs their tumors just disappear. It's incredible and up until now unimaginable for these late stage solid cancers. Similarly, to have people with leukemias who previously we use essentially 40 year old drugs, now we can fight and fight to keep alive long enough to get their T-cells harvested and re-engineered and re-infused and then (after nursing them through a cytokine storm) they emerge... with their cancer wiped out completely. (The article blithely says "remissions measured not in extra weeks or months of life, but in lifetimes". It's a little over-reaching since we just don't have that much long term data yet; these therapies haven't been around for "lifetimes". As a result we often prefer the term "durable remission" to "cure".) I also want to emphasize how few patients have this outcome. It sucks. It sucks to have ads on bus stops and TVs that say, "Ask your doctor about Keytruda", but when they ask me, I know it has such a tiny chance of turning them into that laughing family playing in the grass. We test for and hope for the genetic markers that indicate certain immunotherapies are more likely to work spectacularly, but the vast majority of patients don't have those markers. Similarly, most patients with leukemias or lymphomas do not respond to CAR-Ts. We still try these immunotherapies, though, because there's often evidence of some modest better outcomes, and also sometimes you get lucky. I think I mentioned this on HN in some other context, but one of the breakthrough discoveries around pembrolizumab was because of a "Hail Mary" in late stage colorectal cancer; all the patients progressed & died in the study except for one, and she held the key to the genetic derangement that made that subset of cancer particularly sensitive to checkpoint blockade -- leading to FDA approval for pembro for all cancers with that derangement. As this article mentions, there is now a massive number of trials studying these therapies in various subsets of patients, or in various combinations and permutations with traditional therapy, because short of "cure" there's still improved survival which can often be very meaningful. It's exciting. It's inspiring. It's frustrating & heartbreaking.

Eli_P 8y ago
Could that tech of re-engineering T-cells be a step to cure psoriasis? AFAIK psoriasis is caused by T-cells erroneously targeted to kill epidermis.
- refurb 8y ago
  With the current CAR-T technology, you’re “turning on” the T-cell so it attacks certain cell types. You only need a few of those cells as they can multiply within the body. What you’re talking about is the opposite, turning the T cell “off”. You’d also need to do that to every T cell or alternatively, destroy every T cell and restart with a batch of new cells. Very different problems.
  - WalterSear 8y ago
    Or program the T-cells to attack mesenchymal cells that are producing the defective ones. I'd wager that the process would still be much more difficult than targeting cancerous cells, and certainly be very complicated. But, there's hope for other diseases, though the article is focused on cancer: > Not only can this technology help revolutionize TCR-T cell therapies for cancer, but it will also be a powerful tool for discovering other immunological agents, including antibodies and CAR-T cells, and for elucidating new immunology and cancer biology at a depth not possible before.
- mrfusion 8y ago
  I have an idea for curing psoriasis. It sounds really ridiculous but seeing eating local honey cured my pollen allergies I think it could be worth a try.
  - JPLeRouzic 8y ago
    I am curious about your idea, do you mean that it would be enough to eat honey to cure psoriasis, or is it something else? Thanks!
    - mrfusion 8y ago
wiz21c 8y ago
In aother article pointed by the Guardian, I read : >> Schmid said: “Immune therapy on top of standard chemotherapy prolonged survival by ten months Since, I guess, patient are interested by "being cured", how should I interpret those ten additional months? Of course, I understand the statistic behind it, but I' d like to know if it translates to something meaningful for the life of the patient. For example, if I had a ten month increase in my life, considering that it could mean live 10 month more with pain, false hopes, etc., then I wouldn't feel that the situation has improved meaningfully (of course I don't have cancer and therefore I may miss some obvious benefits). OTOH, if that increase means that the chance of long time remission also increase, then, that's a whole different situation...
- chrisweekly 8y ago
  In my experience as a cancer survivor, it's all about "staying in the game". Medicine doesn't change as fast as software, but extra months means a chance to access new treatment options as they emerge.
  - Ntrails 8y ago
    But for all those who "stay in the game", only a proportion get to survive, and some of those who do not give up meaningful quality of life for 2-3 months more time. Situations are complex and outcomes are highly varied. One size does not fit all.
  - resource0x 8y ago
    I'm another cancer survivor. My understanding is that you don't take this treatment with the goal of surviving extra 10 month. You take in in the hope to be cured, because they say there is a chance, however slim. So the rational choice for me would be: take the treatment, and if in a couple of months it proves ineffective, take euthanasia (if it's legally possible, which is the case where I live - though probably there are still some unfortunate legal caveats), Just hanging around longer would serve no purpose except increasing the pain for my family. (That's my personal view only, not intended as a template for anybody else)
- 8y ago
agumonkey 8y ago
Do you think there's a boon in research that may lead to larger populations responding to immunotherapies ? And if so, should we change protocols to sustain people with incurable tumors just long enough to get a potential treatment ?
gunnr15 8y ago
@doctoring - I am at the early stages of a start-up focusing on oncology. Would love to interview you if you have time. Feel free to reach out to me here: https://www.linkedin.com/in/gunnr/ https://www.linkedin.com/in/gunnr/
kaybe 8y ago
Thank you so much for doing this.
skyfly 8y ago
Is there any evidence that as these techniques are refined we can find ways to apply them to more people OR is it just a matter of your cancer having mutation X or not, no way around it. I’m thinking about Judy Perkins and how her success with stage 4 breast cancer.
mockindignant 8y ago
I am set to start treatment with Keytruda on Friday. I was fortunate that my tumor marker burden (TMB) was/is sufficiently high enough to get me into the clinical trial. I was equally fortunate that 1.) my oncologist is knowledgeable about all of these cutting edge therapies and 2.) my insurance will actually cover the cost. Without the possibility of trying this my options would probably be dying slowly over the next couple of years or doing a very risky surgery that involves opening up my abdomen, cutting out as much of the disease as they can see and flooding the cavity with broad spectrum chemo (HIPEC.) Obviously, immunotherapy is much more palatable as the chemo was not pleasant. Overall I am hopeful. I guess I don't really have a reason to post any of this, other than it helps to get it out there, so please excuse my rambling! And thanks for reading.
- Sinidir 8y ago
  Godspeed
- gjreda 8y ago
  > I guess I don't really have a reason to post any of this, other than it helps to get it out there I know that feeling well. Best of luck to you.
- eyeundersand 8y ago
  Thank you for sharing. All the best for your treatment. :)
- Balgair 8y ago
  My FIL has/had multiple melanoma. One of the tricks for him is his support group. They swap treatment research, good local doctors, emotional support, and when things get bad, they help out in the hospital with nurses, food-runs, etc. Please consider joining a support group. Some are better than others, so feel free to try more than one out and see which one works for you. Oh, and Fuck Cancer.
kevin_b_er 8y ago
Assuming anyone can afford these therapies.
andreygrehov 8y ago
Thank you for such a detailed answer. I'm not an expert by any means, have just a random question. Is it possible to transport markers from people who have them to those who don't? I have zero clue what I'm talking about, but this is the first thought came to my mind and I was too curious not to ask.
- 738472527784 8y ago
  As far as I know, 'markers' reflect metabolic/functional attributes in malignant cells. The question about any type of cancer is wether you can target the malignant cells somewhat exclusively or not. Does the cancer retains healthy features as pathways to cell arrest or apoptosis? Is its metabolism so rapid, to make it's growth distinct over a certain time frame? Is its growth influenced by external signalling? Can the immune system find the malignant cells? The problem really is that cancer is often very heterogeneous, which means a targeted treatment might not kill all of it, leading to evolutionary drive and resistant reoccurrence. The more control mechanisms lost, the wilder the mutations. So worst case, you got cells that behave nothing like a normal cells, but generally can't be distinguished/targeted on a cellular level AND are not localized lesions anymore. So, no, I don't think so. To theoretically transfer a distinct marker to all cancer cells, you'd need a distinct target in the first place.
jillesvangurp 8y ago
Very inspiring indeed. If I live long enough, I'll have lived through a period where most things that killed off my grand parents generation are in principle possible to treat. My impression is that if I manage another 20 years or so, my risk profile for dying of things that currently very common causes of death (i.e. likely to kill me), will have changed completely. That's long enough for me but may not be long enough for people I care about. I'll spare you the cliches; we all know people that died of something (or are dying of something). But it is very heartbreaking to know about people suffering right now when the cure for what is killing them might be just around the corner.
- SlipperySlope 8y ago
  Longevity escape velocity https://en.wikipedia.org/wiki/Longevity_escape_velocity https://en.wikipedia.org/wiki/Longevity_escape_velocity One hopes.

Eli_P 8y ago

Could that tech of re-engineering T-cells be a step to cure psoriasis? AFAIK psoriasis is caused by T-cells erroneously targeted to kill epidermis.

refurb 8y ago
With the current CAR-T technology, you’re “turning on” the T-cell so it attacks certain cell types. You only need a few of those cells as they can multiply within the body. What you’re talking about is the opposite, turning the T cell “off”. You’d also need to do that to every T cell or alternatively, destroy every T cell and restart with a batch of new cells. Very different problems.
- WalterSear 8y ago
  Or program the T-cells to attack mesenchymal cells that are producing the defective ones. I'd wager that the process would still be much more difficult than targeting cancerous cells, and certainly be very complicated. But, there's hope for other diseases, though the article is focused on cancer: > Not only can this technology help revolutionize TCR-T cell therapies for cancer, but it will also be a powerful tool for discovering other immunological agents, including antibodies and CAR-T cells, and for elucidating new immunology and cancer biology at a depth not possible before.
mrfusion 8y ago
I have an idea for curing psoriasis. It sounds really ridiculous but seeing eating local honey cured my pollen allergies I think it could be worth a try.
- JPLeRouzic 8y ago
  I am curious about your idea, do you mean that it would be enough to eat honey to cure psoriasis, or is it something else? Thanks!
  - mrfusion 8y ago

wiz21c 8y ago

In aother article pointed by the Guardian, I read : >> Schmid said: “Immune therapy on top of standard chemotherapy prolonged survival by ten months Since, I guess, patient are interested by "being cured", how should I interpret those ten additional months? Of course, I understand the statistic behind it, but I' d like to know if it translates to something meaningful for the life of the patient. For example, if I had a ten month increase in my life, considering that it could mean live 10 month more with pain, false hopes, etc., then I wouldn't feel that the situation has improved meaningfully (of course I don't have cancer and therefore I may miss some obvious benefits). OTOH, if that increase means that the chance of long time remission also increase, then, that's a whole different situation...

chrisweekly 8y ago
In my experience as a cancer survivor, it's all about "staying in the game". Medicine doesn't change as fast as software, but extra months means a chance to access new treatment options as they emerge.
- Ntrails 8y ago
  But for all those who "stay in the game", only a proportion get to survive, and some of those who do not give up meaningful quality of life for 2-3 months more time. Situations are complex and outcomes are highly varied. One size does not fit all.
- resource0x 8y ago
  I'm another cancer survivor. My understanding is that you don't take this treatment with the goal of surviving extra 10 month. You take in in the hope to be cured, because they say there is a chance, however slim. So the rational choice for me would be: take the treatment, and if in a couple of months it proves ineffective, take euthanasia (if it's legally possible, which is the case where I live - though probably there are still some unfortunate legal caveats), Just hanging around longer would serve no purpose except increasing the pain for my family. (That's my personal view only, not intended as a template for anybody else)
8y ago

agumonkey 8y ago

Do you think there's a boon in research that may lead to larger populations responding to immunotherapies ? And if so, should we change protocols to sustain people with incurable tumors just long enough to get a potential treatment ?

gunnr15 8y ago

@doctoring - I am at the early stages of a start-up focusing on oncology. Would love to interview you if you have time. Feel free to reach out to me here: https://www.linkedin.com/in/gunnr/ https://www.linkedin.com/in/gunnr/

kaybe 8y ago

Thank you so much for doing this.

skyfly 8y ago

Is there any evidence that as these techniques are refined we can find ways to apply them to more people OR is it just a matter of your cancer having mutation X or not, no way around it. I’m thinking about Judy Perkins and how her success with stage 4 breast cancer.

mockindignant 8y ago

I am set to start treatment with Keytruda on Friday. I was fortunate that my tumor marker burden (TMB) was/is sufficiently high enough to get me into the clinical trial. I was equally fortunate that 1.) my oncologist is knowledgeable about all of these cutting edge therapies and 2.) my insurance will actually cover the cost. Without the possibility of trying this my options would probably be dying slowly over the next couple of years or doing a very risky surgery that involves opening up my abdomen, cutting out as much of the disease as they can see and flooding the cavity with broad spectrum chemo (HIPEC.) Obviously, immunotherapy is much more palatable as the chemo was not pleasant. Overall I am hopeful. I guess I don't really have a reason to post any of this, other than it helps to get it out there, so please excuse my rambling! And thanks for reading.

Sinidir 8y ago
Godspeed
gjreda 8y ago
> I guess I don't really have a reason to post any of this, other than it helps to get it out there I know that feeling well. Best of luck to you.
eyeundersand 8y ago
Thank you for sharing. All the best for your treatment. :)
Balgair 8y ago
My FIL has/had multiple melanoma. One of the tricks for him is his support group. They swap treatment research, good local doctors, emotional support, and when things get bad, they help out in the hospital with nurses, food-runs, etc. Please consider joining a support group. Some are better than others, so feel free to try more than one out and see which one works for you. Oh, and Fuck Cancer.

kevin_b_er 8y ago

Assuming anyone can afford these therapies.

andreygrehov 8y ago

Thank you for such a detailed answer. I'm not an expert by any means, have just a random question. Is it possible to transport markers from people who have them to those who don't? I have zero clue what I'm talking about, but this is the first thought came to my mind and I was too curious not to ask.

738472527784 8y ago
As far as I know, 'markers' reflect metabolic/functional attributes in malignant cells. The question about any type of cancer is wether you can target the malignant cells somewhat exclusively or not. Does the cancer retains healthy features as pathways to cell arrest or apoptosis? Is its metabolism so rapid, to make it's growth distinct over a certain time frame? Is its growth influenced by external signalling? Can the immune system find the malignant cells? The problem really is that cancer is often very heterogeneous, which means a targeted treatment might not kill all of it, leading to evolutionary drive and resistant reoccurrence. The more control mechanisms lost, the wilder the mutations. So worst case, you got cells that behave nothing like a normal cells, but generally can't be distinguished/targeted on a cellular level AND are not localized lesions anymore. So, no, I don't think so. To theoretically transfer a distinct marker to all cancer cells, you'd need a distinct target in the first place.

jillesvangurp 8y ago

Very inspiring indeed. If I live long enough, I'll have lived through a period where most things that killed off my grand parents generation are in principle possible to treat. My impression is that if I manage another 20 years or so, my risk profile for dying of things that currently very common causes of death (i.e. likely to kill me), will have changed completely. That's long enough for me but may not be long enough for people I care about. I'll spare you the cliches; we all know people that died of something (or are dying of something). But it is very heartbreaking to know about people suffering right now when the cure for what is killing them might be just around the corner.

SlipperySlope 8y ago
Longevity escape velocity https://en.wikipedia.org/wiki/Longevity_escape_velocity https://en.wikipedia.org/wiki/Longevity_escape_velocity One hopes.