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Immunotherapy, Jimmy Carter's new cancer treatment, explained
Vox ^ | August 21, 2015 | Julia Belluz

Posted on 08/22/2015 9:21:12 AM PDT by Tired of Taxes

At a press conference today, former President Jimmy Carter revealed the ways he is tackling the melanoma cancer that has spread to his brain and liver: He'll receive radiation, as well as another lesser-known treatment called immunotherapy.

Up until now, most cancer patients only had a few options. They could get chemotherapy or radiation that kills cancerous cells and stops them from dividing, or surgery to cut out the disease. Yet the success rate of these options is far from perfect.

Now a new kind of cancer treatment has come into play: immunotherapies. These treatments, which include Carter's infusion called pembrolizumab, try to stimulate the immune system, often through artificial proteins or vaccines, to help the body attack cancer from within.

The positive outcomes for some patients receiving immunotherapy seem extremely impressive. Doctors have seen deadly tumors disappear, and patients who were supposed to die have gone into remission for years. Such prolonged responses to treatment in very sick patients are almost never seen with chemotherapy.

Drug companies are jumping into the fray to bring new immunotherapies to market. As the Wall Street Journal reported, half of Standard & Poor’s top 10 list of promising drugs for 2015 included cancer immunotherapies. In the bleak landscape for cancer treatment, the news is inspiring.

"These latest immunotherapy drugs," Carter said, "whether alone or in combination with other treatments, seem to be the future of cancer therapy."

But is immunotherapy the holy grail scientists have been searching for, or just the latest in a long line of overhyped cancer fixes that flopped? Here's how doctors think about these drugs.

The idea behind immunotherapy is at least a century old

In the 1890s, a New York surgeon named William Coley noted that a patient's cancer seemed to vanish after he came down with a bacterial infection. Coley thought maybe the bacteria had activated his immune system to fight the cancer.

He wasn't alone. Before him, other doctors had also noted the weird link between infections and spontaneous cancer remissions. So Coley started experimenting by injecting people's tumors with bacteria. He found that the cancer regressed in some of those patients.

While Coley is now regarded as the "father of immunotherapy," his peers simply didn't believe his results. The idea of immunotherapy for cancer fell in and out of favor over the next 100 years, particularly as doctors were having success with radiation and chemo.

Immunotherapy can stop cancer — but it occasionally causes serious problems

Flash forward to 1992, when the first immunotherapy for cancer came on the market. Interleukin-2 (IL-2) was approved by the Food and Drug Administration to treat metastatic renal cell carcinoma, an advanced form of kidney cancer, and, a few years later, to treat advanced melanoma (a deadly skin cancer).

When patients took large doses of IL-2 — a protein that's made during an immune response — their bodies sometimes attacked cancer cells, and the drug appeared to save lives. Mark Gorman, the first patient who got the treatment, survived a cancer that should have killed him within months.

But IL-2 treatment hasn't been completely positive. "Despite its potential for miracles, IL-2 produces complete remission in only around 6 percent of people with melanoma. The treatment kills as many as 2 percent of recipients," a 2014 Nature review on the state of immunotherapy notes.

The therapies work wonders for some — but can kill in rare cases

That seems to be a consistent pattern. Doctors have found that immunotherapies can work wonders in a minority of patients with particular cancers. But they often don't work at all in other patients, and can even send some patients' immune systems into overdrive, causing autoimmune disorders that attack healthy cells. In very rare cases, these treatments can kill.

As Heidi Ledford, the author of the Nature review, states, "After that 1992 approval, researchers and pharmaceutical companies spent years trying to develop new immunotherapies that could produce success stories like Gorman's [the IL-2 patient]. But those attempts failed to live up to their promise in the clinic, leading to decades of frustration."

There are several new immunotherapies now on the market

Right now, many different kinds of immunotherapies for a variety of cancers are in testing. These include treatments that use engineered viruses — HIV, measles, smallpox — to reprogram cells to destroy cancer. (The Vice documentary focuses only on these.) There are also therapeutic cancer vaccines and drugs that get T-cells, the soldiers of the immune system, to work harder to attack cancer.

The types of immunotherapy that appear to be most promising at the moment — the ones that really have the medical community excited — are called "checkpoint inhibitors."

"T-cells are tightly regulated with 'turn on' and 'turn off' signals," explained Dr. Michael Postow, an oncologist who is researching immunotherapies at Memorial Sloan Kettering. Checkpoint proteins do the work of turning them on or off. Checkpoint inhibitors block the body's checkpoint proteins, freeing them to attack cancer.

Even checkpoint inhibitors only work on a fraction of patients, and no one really knows why

One of the first approved checkpoint inhibitors was ipilimumab (brand name Yervoy), an infusion that came to market in 2011 and targets a checkpoint protein called CTLA-4. Ipilimumab was also the first drug to extend the overall survival of patients with advanced melanoma.

The average survival rate for patients on the drug was about 10 months (four months more than those who got a cancer vaccine) — but some people had responses lasting years and counting. Again, however, using the body's immune system to fight cancer isn't always safe: The drug causes severe autoimmune side effects in about 15 percent of patients, and 2 percent (14 people) died as a result of the treatment.

Using the body's immune system isn't always safe

Since 2011, two other drugs have also been approved — nivolumab and pembrolizumab (Carter's medicine) — which target a different molecule, PD-1. These drugs treat advanced melanoma, and nivolumab was also approved for lung cancer.

Drugs targeting the PD-1 pathway have shown responses in a variety of cancers such as melanoma, lung cancer, kidney cancers, bladder cancers, and Hodgkin lymphoma. There are now dozens of clinical trials to test this and other kinds of checkpoint inhibitors for dozens of cancer types.

So these drugs also have promising, but nowhere near perfect, profiles. Take, for example, nivolumab, the checkpoint inhibitor approved for lung cancer. Because the science is new, the long-term data isn't in yet. But so far, researchers found two main effects: Some 15 percent of people saw their cancer shrink away or disappear, and about half of the people who had that response found that it lasted for at least six months.

"Although the fraction of people who respond to these agents is small, the durability of responses when they occur represents a substantial step forward," said Dr. Matthew Hellmann, another Memorial Sloan Kettering oncologist and researcher.

As for side effects, he explained, "The most common experience was that patients feel well. But there can be uncommon side effects, where the immune system attacks other parts of the body — like the thyroid gland — that it shouldn't. In those cases, patients have to be treated with steroids, and some, very rarely, have died."

He continued: "When we talk about using the body’s immune system against cancer, there’s a perception that it is natural and safe." But that isn't always the case.

Research that was recently presented at the American Society of Clinical Oncology meeting in Chicago told a similar story. The New England Journal of Medicine study showed that a combination of two immunotherapies — ipilimumab and nivolumab — and nivolumab alone helped melanoma patients live longer than treatment with ipilimumab only. But a majority of patients (95 percent in the combination group and about 82 percent in the nivolumab group) experienced intense side effects (colitis, diarrhea, and fatigue). Some were so severe, the patients had to discontinue treatment.

Dr. Hellmann has been looking into, among other things, why immunotherapy works better in some patients than in others. He has found that for some immunotherapies, patients who had the most heavily mutated tumors responded best.

This insight has left the field with big questions, including: why do these therapies save some lives and not others? "The critical challenge that we have in the scientific community," said Hellmann, "is to figure out who are the patients most likely to benefit from these treatments and how can we develop better treatments to help those patients less likely to benefit from current immunotherapies."

We're not at the precipice of a "cure"

All the doctors I spoke to were really optimistic about immunotherapies, but had several big caveats.

The dramatic progress has been the simple fact that these drugs work for some periods of time in some patients. And one of the major challenges is to understand why, and who will benefit.

As Dr. Hellmann put it, "I think this is true promise." He pointed to the activity in melanoma research and the three drugs now available to patients. But he also said, "About 15 to 20 percent really benefit from the medicines. It's remarkable — in that the benefit, when it occurs, tends to occur for a long time, but the challenge for us is how you identify those 15 to 20 percent.

"This is the beginning of a really important story," he summed up.

Dr. Padmanee Sharma, a physician-researcher at MD Anderson in Houston, Texas, encouraged patients who are interested to seek out experimental immunotherapies on databases such as clinicaltrials.gov. She said she's never seen anything like the effects immunotherapies are having, but added that it's also very early days, and doctors still need to experiment with combination therapies to find out whether they'd be more effective.

Memorial Sloan Kettering's Dr. Postow said for all the buzz about these drugs right now, there's a lot to be learned: "As excited as we are about this field, we know it doesn't help every patient, and we’re still trying to figure out who it helps, how it helps, and why." He continued: "It’s important for doctors and patients to realize this is not chemo."


TOPICS: Culture/Society
KEYWORDS: cancer; cancercure; cancertherapy; checkpointinhibitors; checkpointproteins; immunotherapy; jimmycartercancer; melanoma
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1 posted on 08/22/2015 9:21:13 AM PDT by Tired of Taxes
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To: Tired of Taxes; AllAmericanGirl44; Armen Hareyan; B4Ranch; Balata; Ban Draoi Marbh Draoi; ...
CANCER WARRIORS PING

This is a ping list for cancer survivors and caregivers to share information. If you would like your name added to or removed from this ping list, please tell us in the comments section at this link (click here). (For the most updated list of names, click on the same link and go to the last comment.)

2 posted on 08/22/2015 9:21:55 AM PDT by Tired of Taxes
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To: Tired of Taxes

No death panel for Jimmah.


3 posted on 08/22/2015 9:22:57 AM PDT by miss marmelstein (Richard the Third: I'd like to drive away not only the Turks (moslims) but all my foes.")
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To: miss marmelstein
The problem is the way he thinks, not the tool with which he thinks .... THAT just manifests the disease
4 posted on 08/22/2015 9:26:25 AM PDT by knarf (I say things that are true ... I have no proof ... but they're true.)
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To: Tired of Taxes

If the good die young....

Jimmah Carter is probably gonna end up damned near immortal...

God never wanted him and the Devil hates competition.


5 posted on 08/22/2015 9:30:42 AM PDT by GraceG (Protect the Border from Illegal Aliens, Don't Protect Illegal Alien Boarders...)
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To: Tired of Taxes

Isn’t Jimmy lucky that he doesn’t have to go through Obamanoncare? A 90-year-old with a melanoma that has metastasized throughout his body? The government would never fork over money for his treatment.


6 posted on 08/22/2015 9:31:43 AM PDT by American Quilter (The urge to save humanity is nearly always a cover for the urge to rule. - H.L. Mencken)
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To: Tired of Taxes

I’ll give him 3 months.


7 posted on 08/22/2015 9:31:49 AM PDT by Sacajaweau
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To: Sacajaweau

It’s sad, any cancer is sad. And if and when he passes on I really hope he can go in peace and know that he was not the worst president.


8 posted on 08/22/2015 9:34:08 AM PDT by lilypad
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To: Tired of Taxes

What’s the over/under on this old Commie?

Yep. I’m mean that way. ;)


9 posted on 08/22/2015 9:36:33 AM PDT by Diana in Wisconsin (I don't have 'Hobbies.' I'm developing a robust Post-Apocalyptic skill set...)
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To: Tired of Taxes

In prostate cancer, the approved immuno process is called Provenge. The company that produces it is in bankruptcy, but they continue to produce it. It provides a minor extension of life, but this is for patients that are the most difficult and desperate.

What they are finding is when they apply this in disease progression earlier and if with other agents, the life extension can be significant. Much research is on combining existing agents, earlier in the progression cycle. Provenge costs 90K, which also is a factor.

Another immuno trigger is intense radiation on a small tumor called SBRT. Even then, less than half of the patients respond. I am one who has had this experience, and it’s way too early to see if it worked.


10 posted on 08/22/2015 9:36:39 AM PDT by cicero2k
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To: miss marmelstein

No indeed, not for Jimmy.
Its just too bad that this 90year old brain cancer patient does not have Obama healthcare advisor Ezekiel Emmanuel as his Doctor.

Maybe Jimmy could persuade Dr Zeke the death angel that 90 year old humans will cling to life if offered any chance to extend it

Maybe Dr Zeke could persuade Jimmy that he already used up his “share” of national health resources, did not qualify for extraordinary lifesaving treatment and should just quit


11 posted on 08/22/2015 9:37:11 AM PDT by silverleaf (Age takes a toll: Please have exact change)
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To: Tired of Taxes

Jimmy Carter is 90. Ezekiel Emanuel says it’s time to go.


12 posted on 08/22/2015 9:38:25 AM PDT by Cowboy Bob (Isn't it funny that Socialists never want to share their own money?)
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To: Tired of Taxes

Let’s compare this protocol with what Obamacare would provide.

And then ask, why the difference?


13 posted on 08/22/2015 9:40:35 AM PDT by exit82 ("The Taliban is on the inside of the building" E. Nordstrom 10-10-12)
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To: Tired of Taxes
Mr. Carter, meet fellow liberal Democrat and Obamacare author Zeke "Why I Hope to Die at 75" Emanuel, M.D.

"By the time I reach 75, I will have lived a complete life. I will have loved and been loved. My children will be grown and in the midst of their own rich lives. I will have seen my grandchildren born and beginning their lives. I will have pursued my life’s projects and made whatever contributions, important or not, I am going to make. And hopefully, I will not have too many mental and physical limitations. Dying at 75 will not be a tragedy. Indeed, I plan to have my memorial service before I die. And I don’t want any crying or wailing, but a warm gathering filled with fun reminiscences, stories of my awkwardness, and celebrations of a good life. After I die, my survivors can have their own memorial service if they want—that is not my business."

"Keytruda ... cost $12,500 a month and Merck says the median usage is 6.2 months, which works out to a $77,500 price tag, or $150,000 on annualized basis."

Seems pretty selfish for Carter to accept this treatment, considering what he and his fellow liberals have been preaching all these years.

14 posted on 08/22/2015 9:43:52 AM PDT by Sooth2222 ("In a democracy people get the leaders they deserve." - Joseph de Maistre, 1753-1821)
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To: miss marmelstein

Wouldn’t it be ironic if cancer specialists were brought in from Israel?


15 posted on 08/22/2015 9:49:47 AM PDT by DPMD
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To: Tired of Taxes
In June, 1998 my brother was diagnosed with Brain Cancer. He was placed on Immunotherapy...

,

.

He died September, 1998.

16 posted on 08/22/2015 9:58:49 AM PDT by MuttTheHoople (Yes, Liberals, I question your patriotism)
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To: cicero2k

Prayers that this treatment has worked for you. God bless.


17 posted on 08/22/2015 10:00:55 AM PDT by Tired of Taxes
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To: Sacajaweau

It’s hard to predict. Untreated 3 months is a reasonable guess, but Pembro’s data is impressive. Carter might last long enough to die as the second worst former president. One variable the article doesn’t discuss is the origin of his melanoma. It’s unknown; they couldn’t find a primary site. That’s not rare with cutaneous origin melanoma, a few percent of the total cases. And IIRC their natural course is better than metastatic melanoma with known primaries. However although I’ve read his primary was unknown I haven’t seen anything written saying we know it came from his skin. Liver, where this first showed up, is a common site for early metastases in ocular melanoma, but not as commonly the first site from cutaneous melanoma. Ocular origin melanoma tends to be genetically different than skin origin melanoma and may do better with different therapy. I trust they checked his eyes as well as his skin when looking for a primary.


18 posted on 08/22/2015 10:01:39 AM PDT by JohnBovenmyer (Obama been Liberal. Hope Change)
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To: Tired of Taxes

I would think a more natural cure like hemlock would relieve us of his pain. Uh, I mean, relieve him of his pain.


19 posted on 08/22/2015 10:09:38 AM PDT by captain_dave
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To: MuttTheHoople

Very sorry about your brother. I pleaded for immunotherapy for my father eight years ago, but the oncologists said it wouldn’t work. He passed on quickly, too.

Since then, this kind of treatment has been gaining ground, though. Maybe science will perfect it. A year or two ago, a family friend in his 40’s received immunotherapy for bladder cancer, and he’s been doing very well.


20 posted on 08/22/2015 10:10:32 AM PDT by Tired of Taxes
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