A treatment that genetically alters a patient's own immune cells to fight cancer has, for the first time, produced remissions in adults with an acute leukemia that is usually lethal, researchers are reporting.
In one patient who was severely ill, all traces of leukemia vanished in eight days.
"We had hoped but couldn't have predicted that the response would be so profound and rapid," said Dr. Renier J. Brentjens, the first author of a new study of the therapy and a specialist in leukemia at Memorial Sloan-Kettering Cancer Center.
The treatment is experimental, has been used in only a small number of patients and did not work in all of them. But experts consider it a highly promising approach for a variety of malignancies, including other blood cancers and tumors in organs such as the prostate gland.
The new study, in five adults with acute leukemia in whom chemotherapy had failed, was published Wednesday in the journal Science Translational Medicine.
The treatment is similar to one that pulled a 7-year-old girl, Emma Whitehead, from death's door into remission nearly a year ago, and it has had astounding success in several adults with chronic leukemia in whom chemotherapy had failed. The treatment regimen that saved Emma and those adults was developed at the University of Pennsylvania.
Related studies have also been done at the National Cancer Institute.
But this cell-therapy approach had not been tried before in adults with the disease that Emma had, acute lymphoblastic leukemia. This type of blood cancer is worse in adults than in children, with a cure rate in adults of only about 40 percent, compared with 80 percent to 90 percent in children.
The disease is not common. Each year in the United States, it affects about 2,400 people older than 20, and 3,600 younger. Although there are fewer cases in adults, there are more deaths: About 1,170 adults die each year compared with 270 deaths in people under 20.
In adults, this type of leukemia is a "devastating, galloping disease," said Dr. Michel Sadelain, the senior author of the new study and director of the Center for Cell Engineering and the Gene Transfer and Gene Expression Laboratory at Memorial Sloan-Kettering Cancer Center in New York.
Patients like the ones in the study, who relapse after chemotherapy, usually have only a few months left, Sadelain said. But now, three of the five have been in remission for five to 24 months. Two others died: One was in remission but died from a blood clot, and the other relapsed. The survivors have gone on to have bone-marrow transplants. Their prognosis is good, but relapse is still possible, and only time will tell.
Experts not connected with the study said it was an important advance in an emerging field.
Dr. Carl June of the University of Pennsylvania, who led the team that treated Emma and the other patients, said, "This is the first report showing some real, clinically beneficial activity in adult acute lymphoblastic leukemia." He said his team was also starting to test its version of the cell therapy on patients with the disease.
Dr. Richard M. Stone, the program director for adult leukemia at the Dana-Farber Cancer Institute in Boston, called the research exciting and said he hoped to begin collaborating with the team at Sloan-Kettering. He has already sent them a patient.
The treatment uses patients' own T cells, a type of white blood cell that normally fights viruses and cancer. The patient's blood is run through a machine that extracts T cells and returns the rest of the blood to the body. Researchers then do some genetic engineering: They use a disabled virus as a "vector" to carry new genetic material into the T cells, which reprograms them to recognize and kill any cell that carries a particular protein on its surface.
The protein, called CD19, is found on B cells, which are part of the immune system. This target was chosen because the patients had a type of leukemia that affects B cells, so the goal was to train the patients' T cells to destroy B cells. Healthy B cells which make antibodies to fight infection would be killed along with cancerous ones, but that side effect was treatable.
"We're creating living drugs," Sadelain said. "It's an exciting story that's just beginning."
One of the sickest patients in the study was David Aponte, 58, who works on a sound crew for ABC News. In November 2011, what he thought was a bad case of tennis elbow turned out to be leukemia. He braced himself for a long, grueling regimen of chemotherapy.
His oncologist, Brentjens, suggested that before starting the drugs, Aponte might want to have some of his T cells removed and stored (chemotherapy would deplete them). That way, if he relapsed, he might be able to enter a study using the cells.
At first, the chemotherapy worked, but by the summer of 2012, while he was still being treated, tests showed that the disease was back.
"After everything I had gone through, the chemo, losing hair, the sickness, it was absolutely devastating," Aponte recalled.
He joined the T-cell study. For a few days, nothing seemed to be happening. Then his temperature began to rise.
He has no memory of what took place during the next week or so, but the journal article where he is Patient 5 reports that his fever spiked to 105 degrees. He was in the throes of a "cytokine storm," meaning that the T cells, in a furious battle with the cancer, were churning out enormous amounts of hormones called cytokines.
Besides fever, the hormonal rush can make a patient's blood pressure plummet and his heart rate shoot up. Aponte was taken to intensive care and treated with steroids to quell the reaction.
Eight days later, his leukemia was gone. Even the doctors were shocked, Brentjens said. They repeated the lab tests just to make sure there was no mistake.
Once he was in remission, Aponte had a bone-marrow transplant, as did three of the other patients in the study.
Another had medical problems that made a transplant impossible, and it was he who relapsed and died. The researchers think he might have relapsed because the steroids he needed to treat the cytokine storm might have wiped out the T cells before they could do their job.
For the other patients, it is not known whether the transplants were really needed; in theory, the T cells alone might have produced a long-term remission or even a cure.
Patients treated at the University of Pennsylvania were not given transplants, and most have stayed in remission. But the technique used there involves a different viral vector and different genetic programming from the one at Sloan-Kettering.
Brentjens said the T cells are still experimental, whereas transplants are the standard of care in acute leukemia because they have been shown to give many patients the best odds of survival. So the transplants were done for ethical reasons. The study is continuing, and as more patients are treated, answers might emerge as to whether the T cells alone will be enough for some patients.