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Cancer immunotherapy is moving fast. Here’s what you need to know.

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In addition to the resources listed at the bottom of this article, we recommend the LUNGevity Clinical Trial Finder.

Cancer immunotherapy is moving fast. Here’s what you need to know.

By Laurie McGinley | September 28

The idea of using the body's immune system to fight cancer has been around for a century, but only in the past half a dozen years have dramatic breakthroughs begun rocking the medical world.

"That's when the tsunami came," says Drew Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunology at Johns Hopkins University, and those advances are spawning hundreds of clinical trials nationwide, plus generating intense interest from patients, physicians and investors.

Many cancer researchers compare the progress to medical milestones such as the discovery of penicillin or the development of chemotherapy. Over the next decade, the growth in the field will be "exponential," predicts Philip Greenberg, head of the immunology program at the Fred Hutchinson Cancer Research Center. "Making something better is enormously different than making something work that doesn't work."

At the same time, researchers remember the past anti-cancer efforts that fizzled after initially showing promise. That explains the consensus sentiment at this week's international immunotherapy conference in New York: Turning science into cures will take years of perseverance against daunting hurdles.

Here's a primer about new treatments and how they work:

What is cancer immunotherapy?

Immunotherapy is a significantly different approach from conventional treatments such as chemotherapy or radiation. The latter attack the malignancy itself, while immunotherapy aims to empower the immune system to kill it.

Because of the immune system's unique power, says the nonprofit Cancer Research Institute, this therapy could prove a formidable weapon against many kinds of cancer and offer long-term protection with reduced side effects.

Which immunotherapies are sparking excitement? 

Two types of immunotherapy are drawing most of the interest: checkpoint inhibitors, which remove "brakes" from the immune system, allowing it to see and go after cancer; and CAR T-cell therapy, which involves a more customized attack.

"Checkpoint" inhibitors are designed to block the ability of certain proteins to blunt or weaken the response of the immune system so it can't recognize and go after abnormal cells. In normal times, such checkpoint proteins keep the immune system from being too aggressive and damaging the body. But cancer sometimes hijacks them and uses them to suppress the immune system's response to disease.

[Immunotherapy shows promise in increasing numbers of cancers]

The Food and Drug Administration has cleared four checkpoint inhibitors for adults: Yervoy, also known as ipilimumab; Keytruda, or pembrolizumab; Opdivo, or nivolumab, and Tecentriq, or atezolizumab. The drugs are approved for malignancies including melanoma and Hodgkin lymphoma, as well as lung, kidney and bladder cancer. The treatments also are being tested in a wide range of other cancers.

Former president Jimmy Carter was treated with Keytruda, surgery and radiation for advanced melanoma last year. He announced in December that all signs of his cancer had disappeared.

In CAR T-cell therapy, T cells — a key part of the immune system — are removed from a patient, genetically modified in the lab to target a specific cancer and infused back into the person. This treatment, available only in clinical trials, is being tested mainly for leukemia and lymphoma. The Food and Drug Administration is likely to approve the first CAR T-cell treatment next year or in 2018.

Of these two immunotherapy approaches, most research and investor interest is focused on checkpoint inhibitors. That's because they are off-the-shelf treatments that are much easier to administer than customized T-cell therapy, said Crystal Mackall, a former National Cancer Institute researcher who's now leading immunotherapy trials for Stanford University School of Medicine.

What are some of the main challenges in immunotherapy?

Among the biggest challenges are increasing the response rate among patients and turning initial responses into long-lasting remissions. CAR T-cell therapy often produces a high remission rate in blood-disorder trials, but a significant percentage of patients relapse.

Checkpoint inhibitors induce responses — signaling a tumor has been shrunk or stabilized — in an average of just about 20 percent of patients, said oncologist Elizabeth Jaffee, the deputy director of the Sidney Kimmel Comprehensive Cancer Center at Hopkins. Researchers need to understand why only some cases and some cancers respond. Why, for example, the treatment benefits melanoma but not pancreatic cancer. They think the key to improving effectiveness will be coming up with combination treatments, as happened with AIDS. Jaffee points out that the tide was turned against that disease only after researchers figured out how to use a "cocktail" of medications to keep people with HIV from developing AIDS.

Nationwide, combination trials are testing the simultaneous use of two or more checkpoint inhibitors, a checkpoint inhibitor with a CAR T-cell therapy or an immunotherapy plus radiation and chemotherapy. But combining these can increase safety risks.

Jill O'Donnell-Tormey, chief executive of the Cancer Research Institute, said researchers also are trying to understand tumors' "micro-environments," which contain cells and other factors that appear to sometimes suppress the immune system's response to cancer. The institute, along with the American Association for Cancer Research and two European groups, sponsored the three-day conference in New York.

What are immunotherapy's downsides?

By revving up the immune system, immunotherapy can cause sometimes serious damage to healthy tissue and organs. Researchers are working on ways to limit or even reverse the potential toxicity, but much work needs to be done.

CAR T-cell therapy poses two types of safety risks. Almost all patients get sick with flu-like symptoms, including high fever and pain, a week or so after the treatment; some end up in intensive care. The treatment also can cause brain swelling that can be fatal.

[How cancer thwarts immunotherapy]

Yet standard treatments have major side effects as well. Chemotherapy and radiation, when used for children with leukemia, can cause long-term problems such as secondary cancers, infertility and heart damage. In many ways, researchers say, immunotherapy is less toxic over the long term and might eventually be a good first-line alternative to chemo and radiation.

Immunotherapy can carry higher price tags. For example, Merck's checkpoint inhibitor, Keytruda, costs about $150,000 a year. Once CAR T-cell therapies are approved by the Food and Drug Administration, they may cost hundreds of thousands of dollars a year, according to some analysts. If the treatments are used as directed by the agency, chances are good that insurance will pay for at least some of that.

Does immunotherapy work for children?

Immunotherapy in kids is a mixed picture.

Checkpoint inhibitors are only now being tested extensively in children, so it will take time to see how well they work. But very early-stage studies suggest that they may not be as effective as in adults. One theory holds that these drugs work better in cancers with many mutations — and pediatric cancers tend to have many fewer mutations.

CAR T-cell treatment, on the other hand, is being widely tested in children and has shown impressive effectiveness against acute lymphoblastic leukemia, the most common childhood leukemia.

How do I find immunotherapy treatments?

Talk first to your doctor, who should be able to help you find appropriate medication or clinical trials for unapproved treatment. Trials sponsored by the National Cancer Institute can be found at trials.cancer.gov. Studies also are listed on the website ClinicalTrials.gov --though that doesn't signify government endorsement or approval. Another resource is the Cancer Research Institute's Clinical Trial Finder. 

This story was published on washingtonpost.com on 9/28/16. Link: https://www.washingtonpost.com/news/to-your-health/wp/2016/09/28/cancer-immunotherapy-is-moving-fast-heres-what-you-need-to-know-now/

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