Former president Jimmy Carter, who disclosed in 2015 that he had advanced melanoma, was treated with surgery, radiation and an immunotherapy drug. In December, he said his cancer had disappeared. (Elise Amendola/Associated Press)

This post has been updated. 

The idea of using the body’s immune system to fight cancer has been around for more than a century, but dramatic breakthroughs have occurred only in the past half-dozen years.

“That’s when the tsunami came,” says Drew Pardoll, director of the Bloomberg-Kimmel Institute for Cancer Immunology at Johns Hopkins University. Advances are spawning hundreds of clinical trials nationwide and generating intense interest from patients, physicians and investors. Yet researchers say the treatments, for now, help only a minority of patients. And they remember the past anti-cancer efforts that fizzled after initially showing promise — which explains why they say daunting hurdles and years of perseverance are still ahead.

Here’s a primer about the 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 personalized attack.

“Checkpoint” inhibitors are designed to block the ability of certain proteins to 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.

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 FDA is likely to approve the first CAR T-cell treatment next year or in 2018.

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

What are the latest developments?

Some of the biggest news involves the use of Keytruda in lung cancer, which kills almost 160,000 Americans a year. In an international trial invoving the most common type of the disease, the drug outperformed chemotherapy for patients with high levels of a protein, called PD-L1, on their cancer cells.

At one year, for example, 70 percent of the patients in the Keytruda group were alive, compared with 54 percent of the chemo group, researchers said in October. The Keytruda group also experienced significantly fewer side effects. Based on the trial, the FDA approved the drug as a first-line treatment for patients with non-small-cell lung cancer and a high level of the protein. That was the first time that an immunotherapy drug got the green light as an initial treatment for lung cancer.

“It’s a significant breakthrough,” said Neal Ready, an oncologist at the Duke Cancer Institute. “We’re starting to see people with advanced lung cancer who are alive at a year or two years or three years.”

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 — a tumor is 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. The percentage is higher in some cancers, and researchers need to understand why, for example, the treatment benefits patients with melanoma but not pancreatic cancer. They think the key to improving effectiveness will be the development of 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 contracting AIDS.

Nationwide, hundreds of combination trials are underway. They involve the use of two or more checkpoint inhibitors, a checkpoint inhibitor with CAR T-cell therapy or an immunotherapy plus such standard treatments as radiation and chemotherapy. But combining these treatments 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 elements that appear to sometimes suppress the immune system’s response to cancer. She made her remarks at a conference this year in New York that was sponsored by the institute, along with the American Association for Cancer Research and two European groups.

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 flulike 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.

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.

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 FDA, 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 the most common childhood leukemia, called acute lymphoblastic 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.

Read more:

Immunotherapy is latest weapon against lung cancer

Family hopes immunotherapy will save young girl with tumor

Long-term survival rates lengthen for melanoma patients on immunotherapy

Brain cancer replaces leukemia as leading cause of cancer deaths in children