Hello all. There was an excellent article in the New York Times this week about the immune therapy treatment I am currently receiving at Duke. The drug that I have been given (actually it is an anti-body) is called Ipilimumab and is mentioned in the article.
As I mentioned in my previous post, I will be at Duke next week for radio surgery on the tumor in my brain. The reason that I am being treated separately for the brain tumor is that the Ipilimumab, being an antibody, has difficulty bridging the brain blood barrier which exists to prevent nasty viruses and bacteria from getting at our grey matter.
It is good to know that I am at the forefront of cancer research and that this type of treatment has the potential of offering successful treatment in the future not only for melanoma but for many other cancers as well.
New York Times
October 14, 2013
Breaking Through Cancer’s Shield
By GINA KOLATA
For more than a century, researchers were puzzled by the uncanny ability of cancer cells to
evade the immune system. They knew cancer cells were grotesquely abnormal and should be
killed by white blood cells. In the laboratory, in Petri dishes, white blood cells could go on the
attack against cancer cells. Why, then, could cancers survive in the body?
The answer, when it finally came in recent years, arrived with a bonus: a way to thwart a
cancer’s strategy. Researchers discovered that cancers wrap themselves in an invisible
protective shield. And they learned that they could break into that shield with the right drugs.
When the immune system is free to attack, cancers can shrink and stop growing or even
disappear in lucky patients with the best responses. It may not matter which type of cancer a
person has. What matters is letting the immune system do its job.
So far, the drugs have been tested and found to help patients with melanoma, kidney and lung
cancer. In preliminary studies, they also appear to be effective in breast cancer, ovarian cancer
and cancers of the colon, stomach, head and neck, but not the prostate.
It is still early, of course, and questions remain. Why do only some patients respond to the new
immunotherapies? Can these responses be predicted? Once beaten back by the immune
system, how long do cancers remain at bay?
Still, researchers think they are seeing the start of a new era in cancer medicine.
“Amazing,” said Dr. Drew Pardoll, the immunotherapy research director at Johns Hopkins
School of Medicine. This period will be viewed as an inflection point, he said, a moment in
medical history when everything changed.
“A game-changer,” said Dr. Renier J. Brentjens, a leukemia specialist at Memorial Sloan-
Kettering Cancer Center.
“A watershed moment,” said his colleague, Dr. Michel Sadelain. (Both say they have no financial
interests in the new drugs; Dr. Pardoll says he holds patents involving some immunotherapy
drugs, but not the ones mentioned in this article.)
Researchers and companies say they are only beginning to explore the new immunotherapies
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and develop others to attack cancers, like prostate, that seem to use different molecules to
evade immune attacks. They are at the earliest stages of combining immunotherapies with
other treatments in a bid to improve results.
“I want to be very careful that we do not overhype and raise patients’ expectations so high that
we can never meet them,” said Dr. Alise Reicin, a vice president at Merck for research and
development.
But the companies have an incentive to speed development of the drugs. They are expected to
be expensive, and the demand huge. Delays of even a few months means a huge loss of potential
income.
Nils Lonberg, a senior vice president at Bristol-Myers Squibb, notes that immunotherapy
carries a huge advantage over drugs that attack mutated genes. The latter approach all but
invites the cancer to escape, in the same way bacteria develop resistance to antibiotics.
By contrast, immunotherapy drugs are simply encouraging the immune system to do what it is
meant to do; it is not going to adapt to evade the drugs.
“We are hoping to set up a fair fight between the immune system and the cancer,” Dr. Lonberg
said.
Lowering Defenses
The story of the new cancer treatments started with the discovery of how cancers evade
attacks. It turned out that they use the body’s own brakes, which normally shut down the
immune system after it has done its job killing virus-infected cells.
One braking system, for example, uses a molecule, PD-1, on the surface of T-cells of the
immune system. If a target cell has molecules known as PD-L1 or PD-L2 on its surface, the Tcell
cannot attack it.
So some cancer cells drape themselves in those molecules. The effect, when T-cells are near, is
like turning off a light switch. The T-cells just shut down.
Cancers that do not use PD-L1 or PD-L2 are thought to use other similar systems, just starting
to be explored. Body systems have a lot of redundancy to tamp down immune attacks. But for
now, the PD system showed researchers how cancer cells can evade destruction.
“That is what has been realized in the past few years,” said Ira Mellman, vice president of
research oncology at Genentech. “Tumor cells are making use of this brake.”
The discovery led to an idea: Perhaps a drug that covered up any of those PD molecules, on the
cancer cells or on white blood cells, would allow the immune system to do its job.
(There is another immunotherapy strategy — to take white blood cells out of the body and
program them with genetic engineering to attack a cancer. Studies have just begun and are
promising. But researchers note that this is a very different sort of treatment that is highly
labor-intensive and has been successful so far in only a few types of cancer.)
The first indication that a cancer’s protective shield might be breached came in 2010, after a
trial of the drug ipilimumab in patients with otherwise untreatable melanoma. The drug
unleashes the immune system, letting it overwhelm tumors even if they have a protective
shield.
Patients who took the drug survived an average of 10 months, or 4 months longer than those
randomly assigned to a different treatment. And about 20 percent of patients who responded
have now survived up to 10 years. It was the first drug to improve survival for patients with
metastatic melanoma in a randomized trial.
“It was spectacular,” said Dr.Axel Hoos, vice president for oncology research and development
at GlaxoSmithKline, who helped develop the drug when he was at Bristol-Myers Squibb. “Until
that tipping point, immunotherapy had a bad name. It didn’t work.”
The drug was approved for melanoma in March 2011, with a high price tag — $120,000 for a
course of therapy.
It had another drawback. By unleashing the immune system, it sometimes led to attacks on
normal cells. In some cases, the reaction was fatal. But the trial was a proof of concept. It
showed that cancers can succumb to an attack by the immune system.
“That opened the door a crack,” said Dr. Pardoll, of Johns Hopkins. “People stood up and took
notice.”
A Signal Emerges
Dr. Suzanne Topalian, a professor of surgery and oncology at Johns Hopkins, was one of the first
to test the new drugs in patients. The trial began in 2006, with 39 patients who got a PD-1
blocker, made by Medarex, since bought by Bristol-Myers Squibb. The study included patients
with a variety of advanced cancers, who had failed all traditional treatments; most had tried at
least three, without any luck.
The study looked at safety, not effectiveness. But Dr. Topalian noticed something intriguing.
One patient with lung cancer treated at a collaborating medical center had a partial regression
of her tumor.
“It was very temporary; it was not enough to call it a response,” Dr. Topalian said. “But it was a
signal; it was there.”
That was surprising because researchers had assumed the cancers most vulnerable to an
immune system attack were melanoma and kidney cancer. Lung cancer was supposed to be out
of the question.
“Julie and I got on the phone with Medarex and said, ‘You have to include lung cancer in your
next clinical trial,’ ” Dr. Topalian said, referring to her colleague Dr. Julie Brahmer.
That led to studies of two Bristol-Myers drugs: one that blocks PD-1 and another that blocks
PD-L1. The studies included a 503 patients with a variety of advanced cancers who had
exhausted other options.
The findings, presented in October last year at a meeting of the American Society of Clinical
Oncology, were striking. A significant proportion of patients responded, including 18 percent of
76 lung cancer patients who got the PD-1 drug and 10 percent of 49 who got PD-L1 drug. Dr.
Pardoll, who is married to Dr. Topalian, said that when she and her colleagues presented the
data, “it was almost like a hush fell over the room: ‘Can this really be?’ ”
Emblems of Hope
As researchers continue to study the new drugs and ask if they can improve their results by
combining them with other therapies, they are heartened by some of the rare patients whose
cancers were halted by the drugs. They caution that these patients are unusual; critical studies
to reveal the drugs’ effects on populations of cancer patients are still under way.
“What you really want to know,” said Dr. Roger M. Perlmutter, the president of Merck
Research Laboratories, “is, are people living longer?” For that, “you just have to wait,” he
continued, adding, “What I don’t want to do is give people false hope.”
But some patients, like two treated at Hopkins, have become emblems of hope.
In 2007, M. Dennis Sisolak, who is 72 and a retired engineer from Bel Air, Md., learned he had
kidney cancer. The tumor was huge, and the cancer had spread. After he tried two new drugs to
no avail, his doctor, Dr. Charles G. Drake, a kidney cancer specialist at Johns Hopkins, enrolled
him in an early phase clinical trial of a PD-1 inhibitor. His cancer disappeared on scans and has
not returned, even though he has had no treatment for a year.
“I have a lot of people praying for me,” Mr. Sisolak said.
Dr. Drake said three of his patients had similar responses, including one who was treated five
years ago in the first study. All, with advanced disease, would have been dead by now, he said,
adding, “I have never seen anything like this, personally.”
David Gobin, 63, a retired Baltimore police officer, has a similar story. He learned he had lung
cancer in 2008. He had surgery to remove the two lower lobes of his right lung, then radiation
and chemotherapy.
The treatment was grueling: he lost 70 pounds. Two years later, the cancer was back, and it
had spread to the wall of his chest. He had more surgery, more chemotherapy, more radiation.
In 2010, Mr. Gobin entered a clinical trial of an experimental drug that interferes with cell
growth, but had no success.
Thenhis doctor at Johns Hopkins suggested a Phase 1 trial of an anti-PD-1 drug.
“Sure, I’ll do it,” Mr. Gobin recalled saying. “What do I have to lose?”
His tumors shrank significantly and have not grown, even though he stopped taking the drug
eight months ago.
“Every day I have my feet on the grass is a good day,” Mr. Gobin said. “I was in the right place
at the right time. I will always have cancer, but you know what, I can live with it.
“The Lord wanted me to be alive, and I am alive.”
This article has been revised to reflect the following correction:
Correction: October 17, 2013
An article on Tuesday about new immunotherapies for treating some types of cancer rendered
incorrectly the name of a patient who was undergoing experimental treatment for kidney cancer.
He is M. Dennis Sisolak, not Dennis M. Sisolak. The error was repeated in an accompanying picture
caption.
