He expected to sail through the routine medical tests required to increase his life insurance in October 2014. But the results were devastating. He had lung cancer, at age 53. It had begun to spread, and doctors told him it was inoperable.
A few years ago, they would have suggested chemotherapy. Instead, his oncologist, Dr. Matthew D. Hellmann of Memorial Sloan Kettering Cancer Center in New York, recommended an experimental treatment: immunotherapy. Rather than attacking the cancer directly, as chemo does, immunotherapy tries to rally the patient’s own immune system to fight the disease.
Uncertain, Mr. Cara sought a second opinion. A doctor at another major hospital read his scans and pathology report, then asked what Dr. Hellmann had advised. When the doctor heard the answer, Mr. Cara recalled, “he closed up the folder, handed it back to me and said, ‘Run back there as fast as you can.’”
Many others are racing down the same path. Harnessing the immune system to fight cancer, long a medical dream, is becoming a reality. Remarkable stories of tumors melting away and terminal illnesses going into remissions that last years — backed by solid data — have led to an explosion of interest and billions of dollars of investments in the rapidly growing field of immunotherapy. Pharmaceutical companies, philanthropists and the federal government’s “cancer moonshot” program are pouring money into developing treatments. Medical conferences on the topic are packed.
Cell Wars
Articles in this series are exploring the novel uses of immunotherapy to combat cancer.
Harnessing the Immune System to Fight Cancer
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All this has brought new optimism to cancer doctors — a sense that they have begun tapping into a force of nature, the medical equivalent of splitting the atom.
“This is a fundamental change in the way that we think about cancer therapy,” said Dr. Jedd Wolchok, chief of melanoma and immunotherapeutics services at Memorial Sloan Kettering.
Hundreds of clinical trials involving immunotherapy, alone or combined with other treatments, are underway for nearly every type of cancer. “People are asking, waiting, pleading to get into these trials,” said Dr. Arlene Siefker-Radtke, an oncologist at the University of Texas M.D. Anderson Cancer Center in Houston, who specializes in bladder cancer.
The immune system — a network of cells, tissues and biochemicals that they secrete — defends the body against viruses, bacteria and other invaders. But cancer often finds ways to hide from the immune system or block its ability to fight. Immunotherapy tries to help the immune system recognize cancer as a threat, and attack it.
Doctors tried a primitive version of immunotherapy against cancer more than 100 years ago. It sometimes worked remarkably well, but often did not, and they did not understand why. Eventually, radiation and chemotherapy eclipsed it.
Researchers are now focused on two promising types of immunotherapy. One creates a new, individualized treatment for each patient by removing some of the person’s immune cells, altering them genetically to kill cancer and then infusing them back into the bloodstream. This treatment has produced long remissions in a few hundred children and adults with deadly forms of leukemia or lymphoma for whom standard treatments had failed.
The second approach, far more widely used and the one Mr. Cara tried, involves mass-produced drugs that do not have to be tailored to each patient. The drugs free immune cells to fight cancer by blocking a mechanism — called a checkpoint — that cancer uses to shut down the immune system.
Side EffectsColitis, joint and muscle pain.
Current StatusAbdominal tumor shrunk by 78 percent, but not gone.
These drugs, called checkpoint inhibitors, have been approved by the Food and Drug Administration to treat advanced melanoma, Hodgkin’s lymphoma and cancers of the lung, kidney and bladder. More drugs in this class are in the pipeline. Patients are clamoring for checkpoint drugs, including one, Keytruda, known to many as “that Jimmy Carter drug” which, combined with surgery and radiation, has left the former president with no sign of recurrence even though melanoma had spread to his liver and brain.
Checkpoint inhibitors have become an important option for people like Mr. Cara, with advanced lung cancer.
“We can say in all honesty to patients, that while we can’t tell them we can cure metastatic lung cancer right now, we can tell them there’s real hope that they can live for years, and for a lot of patients many years, which really is a complete game-changer,” said Dr. John V. Heymach, a lung cancer specialist and chairman of thoracic/head and neck medical oncology at M.D. Anderson.
Yet for all the promise and excitement, the fact is that so far, immunotherapy has worked in only a minority of patients, and researchers are struggling to find out why. They know they have their hands on an extraordinarily powerful tool, but they cannot fully understand or control it yet.
One Patient’s Story
Mr. Cara, an apparel industry executive from Bridgewater, N.J., had non-small-cell lung cancer, the most common form of the disease. The diagnosis shattered what had been an idyllic life: a happy marriage, sons in college, a successful career, a beautiful home, regular vacations, plenty of golf.
In December 2014, he began treatment with two checkpoint inhibitors. They cost about $150,000 a year, but as a study subject he did not have to pay.
These medicines work on killer T-cells, white blood cells that are often described as the soldiers of the immune system. T-cells are so fierce that they have built-in brakes — the so-called checkpoints — to shut them down and keep them from attacking normal tissue, which could result in autoimmune disorders like Crohn’s disease, lupus or rheumatoid arthritis. One checkpoint stops T-cells from multiplying; another weakens them and shortens their life span.
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As the name suggests, checkpoint inhibitors block the checkpoints, so cancer cannot use them to turn off the immune system.
Mr. Cara took drugs to inhibit both types of checkpoints. Every two weeks, he had intravenous infusions of Yervoy and Opdivo, both made by Bristol-Myers Squibb. He had no problems at first, just a bit of fatigue the day after the infusion. He rarely missed work.
But turning the wrath of the immune system against cancer can be a risky endeavor: Sometimes the patient’s own body gets caught in the crossfire. About two months into the treatment, Mr. Cara broke out in a rash all over his arms, back and chest. It became so severe that he had to go off the drugs. A steroid cream cleared it up and he was able to resume treatment — but with only one drug, Opdivo. Doctors stopped the other in hopes of minimizing the side effects.
DiagnosisNon-small-cell lung cancer, stage 4.
TreatmentOpdivo and Yervoy for two months, starting in December 2014, then Opdivo alone for eight months, followed by lung surgery.
Side EffectsRashes, fatigue, lung inflammation.
Current StatusWell, active and no signs of cancer.
Checkpoint inhibitors can take months to begin working, and sometimes cause inflammation that, on scans early in treatment, can make it look like the tumor is growing. But Mr. Cara’s first scans, in March 2015, were stunning.
His tumor had shrunk by a third.
By August, more than half of the tumor had vanished. The rash came back, however, and worsened. Steroids worked again, but in October a far more alarming side effect set in: breathing trouble.
Doctors diagnosed pneumonitis, a lung inflammation caused by an attack from the immune system — a known risk of checkpoint drugs. Continuing the treatment posed too great a danger.
Mr. Cara stopped the infusions, but the months of treatment seemed to have transformed his cancer to stage 2 from stage 4, meaning that it was now operable. This spring surgeons removed about a third of his right lung, and discovered that the cancer was actually gone.
“No cancer was seen in any of the tissue they took out,” Dr. Hellmann said. “‘One hundred percent treatment effect,’” he read from the pathology report. “It was pretty cool.”
Immunotherapy had apparently wiped out the disease. “It’s amazing. Unbelievable,” Mr. Cara said.