Milton Wright III seemed to finally have his life on track.
After what seemed like endless interruptions to his education, his football career, and his plans to join the Marines, the 20-year-old found his way. He launched a modeling career and appeared in ads for brands including Zumiez and Adidas. He all but forgot he'd ever had cancer.
"I finally felt like things were going in the direction I wanted them to," Wright says.
But 5 years and 2 months into his second remission from acute lymphoblastic leukemia (ALL), Wright slipped on a sidewalk and heard his ribs crack. He walked the few blocks to Seattle Children's Hospital. He had lived nearby since shortly after he was diagnosed with leukemia at age 8. He'd spent several years there in treatment for two bouts of leukemia -- the second when he was 15.
After looking at his ribs and drawing blood, the emergency nurse told Wright to follow up with blood cancer doctors. "That's when I added everything up," he recalls. "The broken ribs, the blood samples. They think I have it again."
Wright knew kids who'd gotten leukemia a third time. "None of them survived. That's when they give you your 6 months. I realized that I was going to die soon."
Wright's doctor, Rebecca A. Gardner, MD, an assistant professor in pediatrics at the University of Washington, did confirm his leukemia was back, but she didn't give him 6 months. As the lead researcher in a new clinical trial, she suggested Wright be the second person to take part. The first person had no remaining signs of leukemia just 9 days after treatment began.
The trial tests a type of immunotherapy, a new wave of treatments that spur the immune system to fight off cancer like it does other illnesses.
Some doctors and scientists call it the pathway to a cure. Among them is Lynn M. Schuchter, MD, chief of hematology/oncology at the University of Pennsylvania. "We are supercharging the immune system," she says. "This brings a totally new dimension to attacking a cancer cell."
To a T
Some cancer cells share traits with healthy cells, which keeps the immune system from detecting them as problems. Wright's immune system learned to spot them. Through Gardner's clinical trial, researchers changed the genes in his T cells -- white blood cells that survey the body for infections and other invaders -- to recognize and attack his leukemia. After researchers remade Wright's cells in the lab, he got them back through an IV. Then everyone waited for him to get a fever, a sign the T cells are working. If doctors can't manage the fever, they might have to kill off the T cells with a different drug and end the cancer treatment.
Two weeks after he got the cells, Wright's fever landed him in intensive care and doctors thought about killing the cells. "I wasn't ready for them to do that. I asked if we could give it another day or two." Two days later, his fever dropped. A few days after that, when he was well enough for a spinal tap to test for leukemia, the cancer was gone.
A year later, it's still hard for Wright to believe. "When I say I'm cured, I don't feel 100% sure. But according to my blood work, they can't find a single cancer cell in my body."
Wright has since had a bone marrow transplant -- another safeguard against relapse. His recovery seems like a miracle to him, but scores of people with this type of leukemia have now gone into remission after similar treatments.
"It's not just a handful of patients. It's an expanding number at multiple centers," says Renier J. Brentjens, MD, PhD, an oncologist at Memorial Sloan Kettering Cancer Center in New York. He has spent 20 years researching ways to get immune cells to fight cancer. "That's often an indication that you're not looking at a one-patient thing or a fluke."
Since 2009, researchers at Sloan Kettering, University of Pennsylvania, and the National Cancer Institute have tried this treatment on about 100 people with ALL. More than 70 have gone into complete remission. Dozens of institutes around the world are still testing forms of this new treatment.
"This is a very, very bad disease. The 3-year overall survival after relapse is less than 10%," Brentjens says. "Most of the patients that we've seen for a 6-month visit after the T-cell therapy are at or past what their expected survival was when they first came into our clinic."
Researchers are also testing how the rebuilt T cells work in people with other types of leukemia, lymphoma, and myeloma -- all blood cancers. "The question is: Can we expand this technology to more common tumors -- colon cancer, ovarian cancer, breast cancer?" Brentjens says. "I don't know. But I think so."
Brake Test
In another form of immunotherapy, researchers attempt to release the "brakes" on the immune system.
Cancer forms in the first place, in part, because the immune system doesn't attack everything that crosses its path. It has brakes, so to speak. Without them, the body would be in a constant state of fever, rash, or other immune response. Researchers are now exploring how to release those brakes for a short time to unleash the immune system on cancer cells without attacking the rest of the body.
"Melanoma has been the poster child for this type of immunotherapy," Schuchter says. This type of treatment shows promise in cancers of the lungs, bladder, and kidneys as well.
The risk, though, is that the immune system could attack normal cells, too. That could lead to problems such as colitis, tears in the intestines, hepatitis, severe skin rash, and inflammation of the pituitary and thyroid glands.
"They are really serious side effects -- manageable but serious," Schuchter says.
Scientists are making and testing other immunotherapies that target different steps in cancer growth and progress. Some people with advanced metastatic melanoma -- the most deadly skin cancer -- go into complete remission after treatment with drugs such as ipilimumab (Yervoy), which release the brakes on the immune system.
By the time Thomas Sasura, a contractor from Broadview Heights, OH, was diagnosed with melanoma at age 55 in late 2010, the cancer had spread to his lungs, liver, and brain. He soon had lumps he could feel in his back and under his arm. Before his last scheduled round of chemotherapy at Cancer Treatment Centers of America Eastern Regional Medical Center in Philadelphia, Sasura and his doctor could still feel some of the lumps in his body.
"That's when he introduced me to Yervoy," Sasura says. The doctor had never prescribed the brand-new drug and warned that he had no idea how it might affect Sasura. But Sasura had nothing to lose. Three weeks after his first 90-minute drip, all the lumps were gone.
"I couldn't believe it. They said it normally takes two or three injections to kick in," he said. Sasura finished the treatment -- four infusions over the course of 12 weeks -- and he has been in remission ever since. Scans still show cancer in his body, but it doesn't grow and it sometimes shrinks.
"Not all patients respond, but for some, all the tumor goes away, which is highly unusual in melanoma," Schuchter says. "We have patients who had metastatic disease, who are now out 4 years without any evidence of melanoma. I'm beginning to use the words ‘possibly cured.'"
Researchers hope to see similar results with other cancers. Current clinical trials with ipilimumab include people with cancers of the breast, lungs, cervix, prostate, head and neck, pancreas, kidneys, and blood. The FDA has approved two new brake-cutting cancer drugs, pembrolizumab (Keytruda) and nivolumab (Opdivo). Others await approval.
Back to the Future
A year or more after immunotherapy, people like Sasura and Wright no longer think about how they'll spend their final days. They get on with their lives. Sasura is back to work remodeling kitchens and bathrooms. Wright got the green light to return to the gym months before most transplant recipients. Back in shape, he wants to return to modeling. "I feel like this treatment worked," Wright says. "I feel I am truly done with this."
