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    • Cancer treatment extended Jimmy Carter’s life before his 100th birthday
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    Cancer treatment extended Jimmy Carter’s life before his 100th birthday

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    Nine years ago, Jimmy Carter held a press conference at the Carter Center in Atlanta to talk about his cancer diagnosis and treatment.

    At 91, Carter explained that a bad cold the previous May had led to a thorough physical examination, which in early August 2015 resulted in a diagnosis of melanoma, an extremely dangerous form of skin cancer. He underwent liver surgery earlier that month and doctors identified four places where the cancer had spread to his brain.

    If his diagnosis had come a few years earlier, he would have had about six months to live.

    Instead, the former president will celebrate his 100th birthday on Tuesday.

    Luck, of course, played a role. But there is no doubt, experts say, that he is alive today thanks to the immunotherapy he received.

    “It’s a bit of a banal term, but in many ways it’s kind of a model for immunotherapy,” says Dr. Stephen Hodi, who directs the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Brigham Cancer Center. Center in Boston. “There were so many problems that he illustrated as a patient.”

    More: Jimmy Carter, America’s longest-living president, has been in hospice care for a year

    At the time, the treatment was a new addition to the cancer arsenal.

    Just four years earlier, the Food and Drug Administration had approved the first so-called checkpoint inhibitor, commonly called ipilimumab. Carter received the second drug, pembrolizumab, which was approved only a year before he received it.

    Now these treatments and other cancer immunotherapies are among the mainstays of cancer care, alongside surgery, chemotherapy and radiation – not only in melanoma, where the approach first took hold, but also in dozens of other tumor types.

    Just like any other patient

    Dr. David Lawson said he treated Carter with pembrolizumab because the former president was still incredibly healthy and resilient at age 91.

    At the August 20 press conference, Carter said his only regret about his cancer treatment was that it could disrupt a planned trip to Nepal on behalf of the charity Habitat for Humanity.

    Lawson, who works at Emory University’s Winship Cancer Institute, said he believes he treated Carter the same way he would have treated anyone else.

    ‘The best favor you can do for a famous patient is to forget that he or she is famous. The cancer doesn’t care,” he said. “I hope this has not led to a change in the way we have treated President Carter. We certainly tried not to allow it, but you never know.”

    Lawson said he stopped Carter’s pembrolizumab after six months, even though he would normally give it for two years. The former president seemed to respond well and was exposed to a lot of people, so Lawson didn’t want him to have a weakened immune system.

    Carter’s treatment came “at the point” when doctors first realized how effective the treatments could be, said Hodi, who conducted the first clinical trials of the drugs.

    When Carter was treated in 2015, Hodi said, it was still unclear whether patients whose cancer had spread to the brain would benefit. The fear was that the drugs would cause brain inflammation and worsen patients’ conditions, while doing nothing about their tumors.

    Research by Hodi and others has now shown that, like Carter, many patients with brain metastases due to melanoma can benefit from checkpoint therapy. But today, Hodi said, he would give most patients both pembrolizumab and the previously approved drug ipilimumab.

    Lawson said he wanted to be aggressive with Carter’s treatment, but not too aggressive.

    “That’s why we stopped (the pembrolizumab),” Lawson said. “You keep worrying, but we got to a point where we thought, ‘He’s probably recovered from this.'”

    Never too old

    Age is not a barrier to treatment with immunotherapies.

    Dr. Antoni Ribas, a melanoma specialist who directs the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, said he has given checkpoint inhibitors to patients as young as 96 or 97 years old.

    Although older people have weakened immune systems, he says, the fact that the drugs can be effective at such advanced ages shows that the immune system remains active throughout life.

    “The fact that people between the ages of 80 and 90 can get rid of metastatic melanoma tells us that the immune system is quite remarkable,” Ribas said. “I wouldn’t underestimate the immune system of a 90-year-old.”

    Still, doctors are more likely to give older patients “drug holidays” if they experience side effects, he said. It is a term that refers to patients taking a break from taking a drug, and can be used to assess how well a therapy might work, alleviate side effects, and more.

    Overall, only about 1 in 20 patients have serious side effects from immunotherapies, with rash and flu-like fatigue being the most common relatively minor factors.

    The “C” word: heal

    In addition to the immunotherapy and liver surgery, Carter also received radiation treatments aimed at the four small tumors in his brain. But Lawson, Hodi and Ribas agree that without the pembrolizumab he wouldn’t have lived much longer than six months.

    “The life expectancy of someone with liver and brain metastases, even after radiation and surgery, would be counted in months,” Ribas said. “Unleashing the immune system can lead to a normal life.”

    Pembrolizumab and ipilimumab – nicknamed ‘pembro’ and ‘ipi’ – are called checkpoint inhibitors because they remove the brake, or checkpoint, that cancer places on the immune system, allowing immunity soldiers to go to work fighting the cancer.

    Other forms of immunotherapy, many of which are still in development, use the immune system in different ways. Some first lure immune soldiers to the tumor site, while others target different immune tools.

    About half of patients with this extremely dangerous form of skin cancer respond well to immunotherapy, according to a study published earlier this month in The New England Journal of Medicine. Of the patients who survived three years without cancer progression, the study found that 96% were still alive seven years later if they had received both ipilimumab and a drug similar to pembrolizumab called nivolumab; 97% lived if they received nivolumab alone, and 88% lived if they received ipilimumab alone.

    Before these immunotherapy drugs, perhaps 1 in 20 patients would have the possibility of living longer than about six months, Ribas said.

    Still, Ribas, like other cancer doctors, doesn’t like to raise unrealistic expectations for his patients: “I think we should start using the word ‘cure’.”

    At this point, Ribas and others expect that what Carter will ultimately die from will not be melanoma.

    Looking ahead

    Researchers are still trying to make immunotherapies work for more melanoma patients and more people with other types of cancer.

    Research is underway into manipulating different aspects of the immune system, combining different therapies at different times, and improving methods to target individual tumors.

    What does Carter’s survival for so long mean for the doctors who have dedicated their careers to caring for patients like him?

    “It makes us look back at the progress in this cancer and how it benefits patients and changes their lives,” Ribas said.

    Hodi added: “It’s amazing and very festive. It’s fantastic.”

    Lawson reflected on his most famous patient.

    “He’s just a great guy, a great person,” Lawson said. “I wish him a happy birthday and many more to come.”

    Karen Weintraub can be reached at [email protected].

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