FDA Approves First Cell-Based Therapy For Cancer (npr.org)

An anonymous reader quotes a report from NPR: The Food and Drug Administration on Wednesday announced what the agency calls a "historic action" -- the first approval of a cell-based gene therapy in the United States. The FDA approved Kymriah, which scientists refer to as a "living drug" because it involves using genetically modified immune cells from patients to attack their cancer. The drug was approved to treat children and young adults suffering from acute lymphoblastic leukemia, a cancer of blood and bone marrow that is the most common childhood cancer in the United States. About 3,100 patients who are 20 and younger are diagnosed with ALL each year. The treatment involves removing immune system cells known as T cells from each patient and genetically modifying the cells in the laboratory to attack and kill leukemia cells. The genetically modified cells are then infused back into patients. It's also known as CAR-T cell therapy.

The treatment, which is also called CTL109, produced remission within three months in 83 percent of 63 pediatric and young adult patients. The patients had failed to respond to standard treatments or had suffered relapses. Based on those results, an FDA advisory panel recommended the approval in July. The treatment does carry risks, however, including a dangerous overreaction by the immune system known as cytokine-release syndrome. As a result, the FDA is requiring strong warnings.

Comments

But why that particular cancer?

[dgatwood]

Let's put this in perspective. ALL already had treatments that put 98% of affected children into remission within a couple of months, with 8% of those eventually relapsing. So 90% are completely cured with existing therapies. There are other cancers where the numbers are an order of magnitude worse. I'm puzzled why the focus seems to be on diseases that medical science has already very nearly cured, rather than the ones that kill most of the people who get them.

Also, is this actually measurably better than existing treatments? If existing treatments fail to produce remission in 2% and allow a relapse in another 8%, you'd expect only about 20% of the patients to be in that 2% group that weren't helped by chemo. So a remission rate of only 83% is probably not statistically significantly different from what they would have gotten if they had used the current generation of chemo, and doesn't necessarily indicate any benefit for people who did not respond to chemo. So this could very well be a no-op, all at a tremendous cost that insurance won't cover (because it is experimental).

I'm not saying that the research isn't valuable, because it is, but in the zero-sum game of medical research, seeing the first approved cell-based cancer treatment be for a disease that is already all but cured just seems bafflingly backwards. I would have expected the first treatments to be for things like pancreatic cancer or mesothelioma or, if you want a childhood cancer with a high case fatality rate, perhaps neuroblastoma. Brain cancers kill significantly more kids than leukemia, despite being much less common.

Re:But why that particular cancer?

[arth1]

Let's put this in perspective. ALL already had treatments that put 98% of affected children into remission within a couple of months, with 8% of those eventually relapsing. So 90% are completely cured with existing therapies. There are other cancers where the numbers are an order of magnitude worse. I'm puzzled why the focus seems to be on diseases that medical science has already very nearly cured, rather than the ones that kill most of the people who get them.

Money. This is a $400,000+ treatment. People are willing to bankrupt themselves for their kids, even if they aren't for themselves.

Re:But why that particular cancer?

[dgatwood]

I don't disagree. Clearly, chemo is a terrible way to cure disease. It's the modern medical equivalent of leeches. But if you're going to spend X dollars finding a cure for something, do you want to pick a disease that makes up 25% of childhood cancer deaths and dropping rapidly (leukemia) or a disease that has caused a consistent 30% of childhood cancer deaths for decades (brain cancer) with minimal progress? Do you want to be one of hundreds of companies in a crowded field for a disease that kills only 10% of the people who get it (and dropping) or the one company that promises possible salvation for a disease that kills 90% of the people who get it?

Re:But why that particular cancer?

[dcollins117]

First off, medical research is in no way a "zero-sum game". Finding an effective treatment for one form of cancer is a good thing. It's a net plus. It in no way detracts from the knowledge we have about other diseases. The progress we have made in this area could very well lead to treatments for all kinds of different illnesses.

There is a lot of medical research being done. Some of it pans out and some of it doesn't. Using this good news as an opportunity to lament about all the diseases we do not currently have a good treatment for gives me great concern about your ability to reason.

Re:But why that particular cancer?

[Anonymous Coward]

Maybe they want to hit a single before they start swinging for the grand slams. Maybe this isn't the best place for sports metaphors. How about "crawl before you walk?" Hmm, maybe baby metaphors aren't any better.

There must be a reason why this particular cancer is "easy" to treat. So, attack that disease with a new technique to prove that (a) the technique works and (b) it doesn't do more harm than good -- because OMG genetic engineering blah blah.

Once you have re-invented the cure for an "easy" flavor of cancer, move on to the more difficult ones.

This seems like a very straightforward plan to me, and one that is more likely to be successful than one that tries to target the most difficult cases first.

Re:But why that particular cancer?

[Cyberax]

Leukemia is one of the "easier" cancers, as it doesn't really form solid tumors and is susceptible to therapeutic agents. You can bet that they're now pursuing cures for more complicated cancers.

Re:But why that particular cancer?

[dgatwood]

First off, medical research is in no way a "zero-sum game". Finding an effective treatment for one form of cancer is a good thing. It's a net plus. It in no way detracts from the knowledge we have about other diseases. The progress we have made in this area could very well lead to treatments for all kinds of different illnesses.

At this point, it is largely a zero-sum game. Every dollar spent on research in one area is a dollar that can't be spent in another area. One disease's gains represent another disease's losses. The exceptions are the additional knowledge of general techniques for doing gene splicing and other similar areas, but that sort of research is sufficiently independent of what disease you're trying to cure that I doubt it is even typically done by the same organizations.

The progress we have made in this area could very well lead to treatments for all kinds of different illnesses.

In general, I would agree, but unfortunately, when you're talking about genetic modifications to human cells, as I understand it, the treatment tends to be highly specific to a single person, forget a single disease. So apart from the basic gene splicing techniques themselves (which are, I think, fairly well understood at this point), these studies basically just teach us whether you can cure a specific strain of a specific cancer in a specific person. If you're going to do an experimental treatment, if you're going to gain roughly the same knowledge either way, it seems like it would make more sense to try it on a strain of cancer that has a 90% chance of killing the person in the next year rather than a 2% chance. That's all I'm saying.

Re:But why that particular cancer?

[Anonymous Coward]

Kids are used by big pharma and the oncologists as guinea pigs. Even when treatments exist with good prognosis, they are pushed to enroll into experimental programs (including clinical trials), where their chances of survival are slimmer. And that, even in developed countries. There was a scandal in France about this a few years ago. Here is one link (in French) http://www.ametist.org/plancancer.php

Re:But why that particular cancer?

[batukhan]

This. I heard that t-cell therapy currently only works on blood cancers. I guess because you can just inject it and it doesn't need targeting

Re:But why that particular cancer?

[Big Hairy Ian]

It's not it's just the first of about 300 individual cancer treatments (All variants of this technique) to get passed the FDA that's all.

Re:But why that particular cancer?

[AmiMoJo]

One disease's gains represent another disease's losses.

Not at all. This technique for this cancer, now proven, will lead to it being adapted for other cancers. No point aiming for the hardest one first, start with an easy one to prove it works reliably and safely and then move on to the harder problems.

as I understand it, the treatment tends to be highly specific to a single person

Indeed, but the most important part of the technique is being able to quickly and relatively cheaply create such a treatment for any given individual.

Re:But why that particular cancer?

[sharky611aol.com]

IAAPHO (I am a pediatric hematologist/oncologist), so take my comments for what they're worth... TL;DR: This is a big freaking deal. To address your points, ALL was the first drug that CAR-T treatment was approved for for several reasons. 1) It's common, so easier to do the trials. 2) It has good data to support the use of immunotherapy (see blinatumumab, inotuzumab ozogamycin), and this therapy is really just the next step in a long line of improvements in immunotherapy. 3) It's got a good target. Almost all Pre-B ALLs express CD19 and downregulation (the main resistance mechanism for immunotherapy) seems rare (but has been documented in relapsed cases). 4) The cure rate is nowhere near as high as you cite for older children and young adults (currently less than 80% for anyone over 13 years.). THIS is actually where most of the use for CAR-T therapy will come from.

The bigger news is that the TECHNOLOGY for this treatment has been FDA approved. Once you have perfected the cell harvesting/transfecting/culturing/infusing process, it's trivial to plug in a different antigen target into the cassette. And in fact, this is already happening on a large scale. Hop on over to clinicaltrials.gov and search for CAR... We've already got some results from GD2 targeting (neuroblastoma), HER2 targeting (breast cancer and osteosarcoma) and IL-13R2 (glioblastoma multiforme) with promising results. And remember, this is just the first generation of CAR-T therapy to make it to the market. As the technology matures the acceptable uses of it will broaden.

Your zero-sum game argument has been sufficiently debunked below. But suffice to say, this is a true breakthrough technology which will have a huge impact on the field for years to come. But you've gotta start somewhere.

(In bigger news, I think this is the first time in my 18+ years on /. that there's been a pediatric cancer article. That should tell you something...)

Re:But why that particular cancer?

[p4nther2004]

-- At this point, it is largely a zero-sum game. Every dollar spent on research in one area is a dollar that can't be spent in another area. One disease's gains represent another disease's losses. The problem is that research isn't targeted like that - especially initial research. This isn't a case where you "put in X dollars" and pop out a result.

Re:But why that particular cancer?

[e_pluribus_funk]

Well, I've done enough casual reading on CAR-T to know that it's being used in clinical trials on pretty much every type of cancer out there, child and adult including solid (and incurable) cancers like pancreatic cancer.

One reason why they may have initially focussed on childhood leukemia is PR: saving children is good PR, and good PR results in more funding which results in more research which ultimately insures the broadest range of therapies released. Another is, it's possible (conjecture here) that the leukemia disease model is very well known compared to other cancers, and so it's an easier initial target. I do know that because leukemia is blood born, drug delivery to target the cancer is easier, and it doesn't form "structures" like some solid tumors do that allow other cancers to hide from immune cells and drug therapies. All of these may have played a factor in selecting leukemia over glioblastoma or other brain tumors.

Re:But why that particular cancer?

[Enigma2175]

Money. This is a $400,000+ treatment. People are willing to bankrupt themselves for their kids, even if they aren't for themselves.

What? Of course people are willing to bankrupt themselves for medical treatment, whether it's for their children or for themselves. Medical bills are the #1 cause of bankruptcy in the US, 62% of ALL bankruptcies are for medical bills (and 78% of those people had some form of health insurance). We are literally killing people and ruining survivor's lives just so the medical insurance company owners can make more profits. Profit is sacrosanct in the US -- single payer will never happen because Congress is owned by these wealthy individuals and they don't take kindly to anyone who messes with their profits.

Re:But why that particular cancer?

[Anonymous Cow Ward]

There are a few reasons; first, ALL in adults is significantly worse than it is in children, and the drug should (and does, in clinical trials so far) work well for them too. Second, relapsed ALL is pretty much impossible to get rid of except for this; it's not a huge population, but there's not much else you can do for them. The 83% response rate is definitely better than historical controls, in the relapsed patients. Lastly, it's an easier target. Solid tumor cancers seem to be harder to attack using CART therapy, so it makes sense to focus on easier targets first, learn from them, and then apply that knowledge to the harder targets.

Re:But why that particular cancer?

[Anonymous Cow Ward]

And they are working on glioblastoma - it's just a much harder target. It doesn't share a single common antigen like ALL does, so you'll need specific CARTs for each antigen, which means you'll have to spend the money on R&D and clinical trials for each one. It's also much harder to get the T cells into the brain (blood-brain barrier and immune privilege) and solid tumors don't respond as well to CART therapy, for reasons that aren't clear yet but probably partially involve the tumor microenvironment.

Re:But why that particular cancer?

[dciman]

From the perspective of a PhD trained cancer researcher, working on drug discovery/development in academia:

The cost might seem high. Some people think the cost is really going to make these types of cellular based therapy difficult to push into wide spread use. I'm more hopeful that new technology will drive down the cost in coming years. The techniques used to make these cells are years old at this point. That's just how long it takes to get things approved and trials conducted.

But remember the following:

1. This isn't (nor would you want it to be) front line therapy. It's for relapsed or non-responsive b-cell ALL. The side effect profile is risky, this therapy can kill a person, and there are life long implications to receiving it.

2. This is the first approved cellular therapy for wide spread use. It cost a massive amount of money to do the research and push this through the approval process. Billion of dollars for a product not very many people will get.

3. It isn't something that can be made and stored on a shelf. They take your cells out, process them, use a retrovirus to insert a new chimeric antigen receptor into them to target B-cells, and then reinfuse that into the patient. It's personalized medicine to the extreme.

3. The facilities to do what's listed in 2 are insanely costly to build and run, as their are extreme biosafety concerns when altering cells and putting them back into a person. The use of retroviruses makes the biosafety converses higher. Newer technologies will improve this aspect, but haven't been vetted and approved yet.

4. There would be many people involved in making these modified T cells, all of whom likely have masters degrees or PhDs. I'm not talking about the research side to develop them... but production. It's that involved.

5. This is in line with or in most cases cheaper than bone marrow transplants, which are fairly common for other cancers.

6. Novartis will only bill for the product if a patient shows a response within 30 days.

7. These patients have essentially few other options and would likely die without this therapy.

Re:Just wait..

[Zontar The Mindless]

My mother is still alive today thanks to this treatment, and no thanks to you.

cure or kill

[turkeydance]

i'd flip that coin

Re:cure or kill

[rtb61]

Sometimes retiring is the better option, rather than being a lab rat for some one else's greed. The way this stuff if being run by for profit corporations is pretty psychopathic. Lying on test results, with holding information, hiding poor results, lawyering up to keep bad treatments going profitably for as long as possible regardless of consequences. Not that this treatment is bad but they have done it to themselves, the typical US corporation is simply no longer to be trusted no matter what they claim to do or claim to be, the end result of modern PR=B$. Is it good, is it bad, yes thanks to endless lies from corporations, it is a fucking coin toss. Executives should start paying a personal price for their lies and corrupt decisions in corporations.

Re:Just wait..

[lucm]

It's amazing to think that one day cancer could be a thing of the past, like smallpox.

Re:Just wait..

[Waffle Iron]

Once it becomes FDA approved and a patent is awarded, one of the big pharma companies will come in with a blank check to the patent owner and will immediately proceed to bury this knowledge and it'll never be used again, all in favor of high-priced chemotherapy.

TFA says that the bill for this one-time treatment weighs in at $475,000. That's probably even more high-priced than almost any chemotherapy.

Re:Just wait..

[Anonymous Coward]

Gleevec, a drug used to treat CML, GIST and HES runs about $7,350.00 for a 30 day supply of 100mg tablets. I've been on Gleevec for roughly 8 years now.

Now, I know that the insurance companies don't pay full price, but if they did, then that 8 years of "treatment" with Gleevec has cost them $705,600.00, and that cost continues until the day I die.

That makes a single payment of 475,000 cheap compared to 30 years of medication at a whopping $2,646,000.00... (if the price remained unchanged)

That means it could work for H.E.S. as well.

[Anonymous Coward]

Hypereosinophilic Syndrome, or HES as it's commonly referred to is a cancer that affects roughly 1 in 18 million people. A bone/blood cancer that causes the marrow to create too many eosinophils. These eosinophils are toxic to the body in that when they die, they go 1 of 3 possible ways, each way killing cells surrounding them. Having been diagnosed with HES almost 8 years ago, after over 4 years of feeling like I'd slept in a bed of poison-ivy while having chicken-pox and a 3rd degree sunburn. At the time of diagnosis, my kidneys were failing, I had heart palpitations, my gall bladder was 4 times normal size from it trying to pull in as many eosinophils as it could, but with counts ranging from 23,000 to 54,000 per unit of blood (normal ranges are from 0 to 400, where 400 is a moderate to severe allergic reaction) there was no chance of it taking in enough to make a difference without destroying itself, and my optic nerves were being hampered with, showing up as ocular migraines, some occurring while operating a motor vehicle. To put it bluntly, I was months from death.
    What saved me? A drug, designed for CML patients, and certain GISTs (gastro-intestinal sarcomas), called Gleevec or Imatinib. Within 2 weeks of starting the chemo, it had my numbers under control.
Now, if this treatment works for Leukemia, I'd imagine it could be used to similar effect with the poorly encoded genetic sequence inside my own bone-marrow.
I look forward to my next appointment with my oncologist.

Patents / Golden-egg-laying geese

[DrYak]

and a patent is awarded,

Most of the individual steps that are involved rely on knowledge that has been published in scientific articles and spoken about in conference (I was there !) and thus constitutes "prior art".

The most expensive part (due to regulation, certification, approval, guarantee, etc.) is putting all the steps together into a process.
And that about the only thing that they can patent (because that one specifically might not have been published) the exact specific steps this process relies on.

Meaning that if such patent-trolling happens, it doesn't prevent any other company to putting together the necessary key steps (which again, are already available published knowledged, not patented) into a slightly different process (and do it enough slightly differently so that it's not covered by the above process) that can be used.

Lastly, TFS make it seem rather simple ("Hey just fix a gene in the white cell, inject it back and problem solved !") whereas in practice, it's extremely complicated and tedious steps.
e.g.: it takes a lot of cultures and trial-and-error until you get the "perfect antibody" that will work, that you can then CISPR-splice back into the patients' white sells.
It's not something that is quickly cobbled by a technician in a clinic's lab, it something that require a crew of biology/immunology university scientists and a whole bio-informatics division (= computers are used to detect potential best targets to accelerate the work of the lab team).

Meaning it's an expensive process.
Meaning that the company that decides to implement this on a large scale commercially has still lots of money to earn (they'll be basically selling the "service" of doing all this tedious steps per patient).
It's *definitely not* going to insta-kill the big pharma's golden-eggs-laying goose. Just replace one goose (chemotherapies manufacturing and selling) by another (service of adapting gene/cell therapies).

Reference points

[DrYak]

The thing is :

- these classes of methods are generic. With very few problems (it's not relying on killing the patient slower than killing the cancer. It's about specifically targetting the cancer) Eventually this method could be adapted to other cancers as well.
so the fact that they used it against leukemia isn't a major drawback for brain cancer.
(Unlike chemotherapies which rely a lot on the general charecteristics of the cancer, to find a way to poison it with a drug faster than the drug posions the rest of the patient. Different type of cancer = different type of characteristics. Poisons will therefore work differently)

- because leukemia is well studied and has already lots of studies done with other treatment, that gives a lot data point to compare against, and to combine with.

- leukemia happens to be a slightly lower hanging fruit here. (everything happens in the blood stream, which is where you'd be injecting the modified cells).
(but again, all fruits *on the same tree*. Not an entirely different tree like chemotherapies).

These are reasons to take it as a first target, before expanding to other cancers.

Re:Just wait..

[K. S. Kyosuke]

I doubt that will happen any time soon. I mean, like most things, the human body can go wrong in many more ways than it can go right, and "cancer" happens to be an umbrella term for like a quarter of those things that can kill you. I've noticed that many such treatments as outlined above are focused on leukemia in particular. Perhaps that's because leukemia seems to be on the opposite side of "curability by modified T-cells" than, say, astrocytoma. It might take a very long time to find out what to do with all cancers that you could possibly get.

Missed clickbait headline opportunity...

[Junta]

'FDA approves new treatment for ALL cancer'

Re:Missed clickbait headline opportunity...

[sacrilicious]

'FDA approves new treatment for ALL cancer'

Indeed, "for ALL disease"

Probably because this form of cancer *IS* so well

[p4nther2004]

studied. You have to remember - just 50 years ago, ALL was pretty much a death sentence and it tends to hit kids more than adults. 2nd - this treatment is used AFTER patients had failed to respond or relapsed. So this treatment this roughly an 85% success rate takes it from 90% to what, an almost 98% success rate (overall)? But the real question (and I haven't seen it answered by anyone yet) is whether or not it'll be effective for Philadelphia chromosome (9/22) patients. (I haven't had a chance to research that yet.) While ALL treatmentment are very good, for ALL Philadelphia patients the prognosis was still poor last I checked.

Follow-up looks like it's still be studied for Phi

[p4nther2004]

Philadelphia positive patients (9/22)

https://clinicaltrials.gov/ct2...

Re:Just wait..

[pablo_max]

TFA says that the bill for this one-time treatment weighs in at $475,000 in America.

Fixed that for you.
For those of you who, for some reason don't see it or refuse to see it, your system is complete and totally shit.
I have close family members who still live the US. One who recently was diagnosed with Cancer. Turns out that the cancer was a result of another illness which went undetected for nearly 20 years.
The medicine for the illness is in excess of 40k per treatment in America. The family member was able to come to the EU country in which I live and paid 1000€ for the non-insurance price to have the doctor give the injections.
The people who support this price gouging system, to mind, are fucking disgusting human beings. If in fact they should even be considered Humans.
What kind of sick fuck literally holds lives hostage in an effort to increase their profits 100 fold?
Worse than ISIS, Hitler, Stalin and Satan combined.

Re:Just wait..

[GLMDesigns]

You're the sick person if you think that price gouging (even at it's worse) is more evil than ISIS, Hitler and Stalin.

Let's see now - actively killing people whose views you don't like - or the worst case of corporate greed. You realize that even the greediest corporation needs customers. They cannot make it so expensive that no one will buy their product.

In fact the economic history shows that volume of sales almost always trumps profit made per sale.

Make a one hundred million sales a day with a profit of one dollar each OR
make one thousand sales a day with a profit of one thousand dollars each?

Which is the more successful company?

Re:Just wait..

[Anonymous Cow Ward]

Is Novartis, the company who licensed it and is producing it, not considered a big pharma company?

Re:Just wait..

[pablo_max]

What ever you say, Hitler.

Re:Just wait..

[Gilgaron]

it'll never go away just because of how cancer works, but the sorts that "aren't a big deal'" will get more broad.

Re:Just wait..

[MrHops]

Once it becomes FDA approved and a patent is awarded, one of the big pharma companies will come in with a blank check to the patent owner and will immediately proceed to bury this knowledge and it'll never be used again, all in favor of high-priced chemotherapy.

TFA says that the bill for this one-time treatment weighs in at $475,000. That's probably even more high-priced than almost any chemotherapy.

I know that this is moving the goalposts a bit, but a very common treatment for leukemia is a stem cell transplant after intensive chemo. That can go well over $1,000,000 all told, more like $2,000,000. Again, that is the listed price, the insurance companies will pay less.

(Don't ask me how I know this... :-( )

Re:Just wait..

[GLMDesigns]

Ha. I'm a Hitler because I think that price gouging is not as horrible as exterminating people as did Hitler, Stalin and Mao.

Add to that that it's clear that I think that price gouging is immoral, and you still equate me to Hitler.

You've jumped the shark. Thank you for so clearly exposing your views.

Re:Just wait..

[lucm]

They're not idiots, they're a symptom that the credibility of the scientific community is not what it used to be. I don't think this is a matter of intelligence as much as it is a matter of social fragmentation.

Re:Just wait..

[micahraleigh]

Although this looks like a very stinging thing to say, in the mentality of /. you are giving this fellow compliment.

They just think there are too many humans on the earth and prolonging life just takes resources from the young, fun people and the government elite.