When old age is a boon: How being 91 helped Jimmy Carter battle cancer
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Former president Jimmy Carter said on Sunday that his cancer is gone, following treatment with a cutting-edge immune-boosting drug.

Carter said in a statement that a recent brain MRI indicated that the four melanoma lesions on his brain were gone and no new ones had formed. The former president said that he will continue to receive doses of Keytruda, a recently approved immunotherapy drug.

Carter broke the news while speaking during a Sunday school class at Maranatha Baptist Church in Plains, Ga., telling an audience that doctors had given him the good news only this week.

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“When I went this week, they didn’t find any cancer at all,” Carter said.

Doctors: You have weeks to live

In August Carter revealed that he had been diagnosed with melanoma, usually a skin cancer but which in some cases affects internal organs, and that it had spread to his liver and brain.

His early prognosis was dire. “I just thought I had a few weeks left. But I was surprisingly at ease,” Carter said at a press conference at the time. “I’ve had a wonderful life, I’ve had thousands of friends, and I’ve had an exciting and adventurous and gratifying existence.”

Carter underwent surgery for the liver tumor, and was treated with radiation therapy as well as four doses of pembrolizumab, which is sold by Merck as Keytruda. The drug is priced at about $12,500 per month.

Last month the Carter Center announced that the former president’s cancer was “responding well to treatment.”

With new drugs, cures in sight

Keytruda received Food and Drug Administration approval in 2014 as a “breakthrough” drug for treatment of advanced melanoma. It is one of a growing number of drugs that fight cancer by blocking proteins that keep cells of the immune system from attacking tumors. By blocking the PD-1/PD-L1 proteins, Keytruda may unleash the body’s immune system to fight malignant cells.

If Carter is indeed cancer-free, his response to Keytruda has been better than that of most patients in the clinical trial that led the FDA to approve the drug.

In a key study, 173 participants with advanced melanoma were treated with Keytruda, either at the standard dose of 2 milligrams per kilogram of body weight (mg/kg) or at five times that dose. Of the participants receiving the standard dose, about one-quarter had their tumors shrink, a response that lasted at least 1.4 to 8.5 months and, for most patients, longer, the FDA said when it approved the drug.

That pattern is typical of cancer drugs that work through the immune system. Most of them help only a minority of patients. But those who respond can experience what seem to be full cures.

Still, the success of the treatment in Carter’s case seems to have exceeded his doctors’ expectations. Walter Curran Jr., executive director of Emory University’s Winship Cancer Institute where Carter was treated, told the Wall Street Journal in August, “We’re not looking for a cure in patients who have a disease like melanoma that has spread.”

A potential for lifelong protection

Often, with standard chemotherapy drugs, cancer cells eventually change in a way that makes them invulnerable to the compounds, such as by developing a mutation that literally pumps the drug out of the cells before it can kill them. A big reason for the excitement over “immuno-oncology” drugs — which have inspired titles in sober medical journals such as “Release the Hounds!”— is that such resistance seems to occur rarely if at all.

Instead, the immune system has a “memory” for its targets, said Dr. Antoni Ribas of the University of California, Los Angeles, who led a key clinical trial on Keytruda. “Once you get the immune system to attack the cancer by preventing what had kept it from doing so, it has a long-lasting effect because the immune system remembers,” he told STAT on Sunday.

Just as a 90-year-old who received a smallpox vaccination decades ago is still protected from that disease, so a cancer patient whose immune system attacks melanoma cells in 2015 is expected to keep doing so essentially forever. That bodes well for Carter’s continued survival, Ribas said: “The immune response can last years.”

“But that response comes in only a minority of patients,” he pointed out. “We’re unleashing the immune system with these drugs,” by removing the molecules that block it, “but there has to be an immune system to unleash, an immune system that’s ready to attack the cancer.”

Age works in Carter’s favor

It might seem surprising that Carter’s age did not work against him. In general, older people have weaker immune systems than younger ones; that’s why standard immunizations such as seasonal flu vaccines tend to be less effective in elderly people than in young adults.

But the opposite may be true in the immune response to melanoma. “Melanomas that develop later in life tend to have more mutations,” Ribas explained, simply because they have had more decades for ultraviolet light to induce those DNA changes. With old chemotherapy drugs, more mutations are bad news: each mutation represents another way that the cancer can elude the drugs. But with immuno-oncology drugs, he said, “the opposite is true: when a melanoma or other cancer has many mutations, it’s more likely that the immune system can attack them.”

Mutations — or changes in the DNA of a tumor cell — often produce molecular markers on the cells’ surface, markers that act as come-hither beacons to immune cells. The more such beacons, the more killer immune cells respond, and the more likely the malignant cells are to be destroyed.

“Before, we all thought that more mutations made a cancer more aggressive,” said Ribas, who is also director of the tumor immunology program area at UCLA’s Jonsson Comprehensive Cancer Center. “Now we know it’s the opposite.”

In fact, scientists were so optimistic that age would not be a barrier to responding well to Keytruda that patients in a clinical trial of the drug were as old as 94, pointed out Dr. John Suh, a radiation oncologist at the Cleveland Clinic.

In contrast to the characteristics of melanomas in older patients, he said, “melanomas in younger patients have fewer mutations, so they may not be recognized by the immune system.” In that case, drugs like Keytruda are expected to be less effective: the drug eliminates the barrier to immune cells, but there are no immune cells that are able to take advantage of the open door.

Although Carter’s immune system, unlocked by Keytruda, is likely the main reason he is cancer-free, he undoubtedly benefited from the high-precision, high-intensity radiation he received to his brain, too. Carter said in August that he had “four spots of melanoma” in his brain, and received so-called stereotactic radiation therapy.

That “may have synergistic effects,” said Suh, so that “the combination of stereotactic radiation and immuno-oncology drugs” is especially beneficial.

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