Will Immunotherapy Be the End of Cancer?
Immunotherapy has been called a great hope—and a great hype. As a patient facing devastating odds, our writer bet her life on it.
In September of 2011, I did the worst Google search of my life. A year after a seemingly manageable melanoma diagnosis and surgery, I learned that my cancer had appeared again, this time moving aggressively into my lungs and soft tissue. Naturally, the first thing I did was open my laptop and type "stage 4 melanoma life expectancy." Then I cried. The results were terrifying.
On the website of MD Anderson, one of the most prestigious cancer centers in the world, I found a January 2011 article on metastatic melanoma. There was a telling quote from Michael Davies, MD, of the center’s Melanoma Medical Oncology Department: "The average survival for patients with stage 4 metastatic melanoma is 6 to 10 months, and this hasn’t changed for 30 years."
I still get chills when I recall my prognosis not so very long ago, a prognosis that looked likely to wipe my presence from my two young daughters’ childhoods. Yet a month after my diagnosis, I became one of the first dozen patients in a new clinical trial at the Memorial Sloan Kettering Cancer Center in New York City, receiving a type of treatment known as immunotherapy, which harnesses the body’s natural defenses to fight cancer. Three months later, I was declared cancer-free, and I have been ever since. I had not only been granted a future—I had seen a glimpse of it. Welcome to the next era of medicine.
WATCH THE VIDEO: "I Survived Stage IV Melanoma"
Our bodies are incredible machines. We are born with an internal defense system designed to fight off invaders like infection and disease. At the heart of that system are T cells, microscopic killers that recognize and destroy abnormalities. But cancer is a potent—and sneaky—foe. "For reasons we are just beginning to understand, your T cells don’t see the cancer cells," explains Naiyer Rizvi, MD, professor of medicine at Columbia University Medical Center and a leading specialist in immunotherapy for lung cancer. And the immune system can’t fight an enemy it doesn’t even recognize.
In the fight against cancer, the trinity of surgery, radiation, and chemotherapy—known by the assertive nickname "slash, burn, and poison"—has long been the weapon of choice. By going directly after cancer cells (almost always with collateral damage to otherwise healthy parts of the body), the method at least has an understandable logic: Scorch the area, then cross your fingers that the disease doesn’t come back.
Immunotherapy approaches the problem differently, stimulating the patient’s own body to kill the cancer. But reprogramming the immune system to, as Dr. Rizvi says, "break the hypnosis effect" that cancer cells have on our T cells has been hard to achieve, and immunotherapy languished for decades as a fringe field of research. I just happened to be lucky enough to be diagnosed with my typically fatal—and historically chemo-resistant—form of cancer at the right time for a breakthrough.
In the spring of 2011, the FDA approved the immunotherapy treatment ipilimumab, known by the brand name Yervoy. It was the first drug proven to extend the lives of patients with metastatic melanoma. That fall, when I needed a Hail Mary pass the most, I joined a clinical trial in which I would be given regular infusions of Yervoy with a new drug, nivolumab. (That drug would be approved under the brand name Opdivo in 2014.)
Cancer cells slip past the immune system by appearing invisible to it. The job of immunotherapy is to activate the system to recognize the enemy. "I tell people, 'This is not a cancer drug; it doesn't kill tumor cells. This is an immune system drug,'" says James P. Allison, PhD, chair of the department of immunology at the University of Texas MD Anderson Cancer Center in Houston. In my case, the hope was that the two drugs would work together to override the breaks holding back my own defenses, flipping the switch on my T cells to go find and kill my cancer.
And my T cells quickly did just that, like Pac-Man devouring pellets. After my very first treatment, a visible tumor under the skin on my back began to shrink. By my first set of scans—only 12 weeks into the trial—all my cancer was gone. And I was not an isolated success case; other patients were showing marked improvement, too.
As the trial expanded, nearly 58 percent of patients had “significant reduction in tumor size,” an achievement my doctor, Memorial Sloan Kettering’s Chief of Melanoma and Immunotherapeutics Service Jedd Wolchok, MD, noted at the time by saying, "Just five years ago, many of these patients would have been expected to live for only seven months following diagnosis." In September of 2015, the one-two punch that saved my life became the first immunotherapy combination treatment to gain FDA approval.
But what makes a story like mine even more mind-blowing is not just that the cancer went away. It’s that four years after I was declared cancer-free and two years after I completely ended treatment, it has not come back. In much the same way that once you’ve been vaccinated, your body recognizes and fends off formidable diseases, the hope of immunotherapy is that when your body has learned to identify your form of cancer, it remains vigilant against it. That’s why some of the currently approved courses of immunotherapy span only a few doses over a relatively short period: The idea is that as soon as the body learns, it remembers.
A life without the constant worry that I’ll get sick again has been the second greatest gift of my treatment. It puts me in a privileged population—a 2013 German study of recent cancer survivors found that more than 67 percent expressed a fear of recurrence. Of course, as one of immunotherapy's relatively recent successes, I know that things could change. But I also know that the early two- and four-year studies on the growing number of people who have had progression-free survival suggest that our responses have been generally durable. As blogger T.J. Sharpe—who, after a stage 4 melanoma diagnosis, has been thriving for three years in a trial of the immunotherapy drug Keytruda—puts it, "The truth is the drug isn’t beating cancer; my immune system is."
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The new hope
With encouraging results like mine, it’s little wonder that in just the past few years, immunotherapy—alone and in combination with traditional methods—has been touted as the next big thing not only for melanoma but for cancer itself. Though other forms of the treatment take different approaches, like modifying and transferring T cells, they have the same goal: lighting up the individual’s own system. Since 2010, the FDA has approved immunotherapy treatments for prostate, kidney and lung cancers.
Meanwhile, clinical trials and research continue to show that immunotherapy holds promise for devastating forms of cancer, including breast, ovarian, and pancreatic cancers and myeloma. "We’re recognizing that the lessons we learned studying the relationship between the immune system and melanoma are applicable to other types of cancer," says Dr. Wolchok. "We’re now engaged in trials spanning 5 to 10 other cancers." Adds Jill O’Donnell-Tormey, PhD, the CEO and director of scientific affairs at the Cancer Research Institute in New York City, "The ultimate potential is that immunotherapy could have an impact on all types of cancer." New research and treatments have also been gaining ground against the notorious immune system foe HIV.
The principles of immunotherapy are not only being used to fight disease; they’re also being applied to preventing it. You’re probably familiar with one example—in 2006, the FDA approved Gardasil, the first of three vaccines that prevent infection with the types of HPV that can cause cervical and anal cancers. Scientists are working on vaccines for breast cancer and lymphoma.
In his final State of the Union address in January, President Barack Obama pledged to support Vice President Joe Biden’s "cancer moonshot," and vowed, "Let’s make America the country that cures cancer once and for all." While cancer has a wide variety of unique manifestations that may never have a single cure, the possibility of profound progress owes a large debt to the explosion of breakthroughs in the field of immunotherapy.
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Facing the future
But while there’s plenty to be excited about, there are still significant downsides. The cost of an approved course of immunotherapy for a late-stage cancer patient can be astronomical; when my drug combo hit the market, it held a price tag of more than $250,000 a year. And though you won’t lose your hair like you might with chemo, immunotherapy is far from a guaranteed "get out of side effects free" card. My course of treatment went relatively smoothly, but the side effects for some—from fever to colitis—can be so severe that they’re unable to continue treatment.
The biggest reality check of all, however, is that the number of cancers immunotherapy has been proven effective for is still relatively small (though growing)—and it doesn’t work on every patient. The fact that more than half the patients on my drug combination, people with serious cancer and alarming odds, had their cancer shrink is incredible. But it’s not what you’d call a decisive victory in the war on cancer.
Last summer, 91-year-old former president and metastatic melanoma patient Jimmy Carter began a course of treatment that included Keytruda. By December, he was sharing the good news that a recent MRI "did not reveal any signs of the original cancer spots nor any new ones." (In March, he announced that he was able to stop treatment.) But two weeks before that, a friend of mine died. We’d both endured melanoma of the scalp and undergone surgery for it. We’d both had a recurrence that catapulted us into late-stage cancer. We had the same doctors. She had just started on the combo that saved my life. It did not save hers. She was 25.
Why did immunotherapy apparently work on Carter and not her? Why is it so effective on some of us and not others? Because cancer doesn’t play fair, and even the most promising treatments don’t work on everybody. T.J. Sharpe says that when he was initially diagnosed, "A doctor told me, ‘Don’t be surprised if you’re not here in two years.’ I know statistically he was right." Yet here he is. Here we are.
That’s the next great mystery. "What is it about the subsets of patients who respond that makes them different?" says Dr. Wolchok. "We are now at the beginning of the journey." Yet it’s one that has already come so far. One I can’t wait to spend my long, long life watching.
Every morning when I wake up, my eyes open to a print that leans against the wall opposite my bed. It reads, "When odds are one in a million, be that one." I have been. But how much more amazing it is, with every new breakthrough, to see myself becoming something else. Not so unique. Just another person who got cancer, and then got better.
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What you need to know about melanoma
Melanoma is the deadliest form of skin cancer, killing more than 10,000 people in the U.S. each year. And the disease is on the rise: The CDC reports that between 1982 and 2011, melanoma rates doubled. While at least part of the problem is environmental (blame decreasing ozone levels), the main risk for melanoma arises from individual predisposition and behavior.
In the hopes of reversing the trend, in 2015 the FDA proposed a nationwide ban on the use of tanning beds for individuals under the age of 18. In the meantime, follow the drill you've likely known ever since you were a kid: Wear sunscreen, ideally a broad-spectrum SPF 30. Reapply regularly. Stay out of the sun during peak midday hours. Wear a hat. You don't need to be obsessigve or avoid your regular activities, but you do need to make friends with common sense and consistency like your life depends on it. It does.