Nov. 4, 2014 -- Twenty-year-old Milton Wright III’s life seemed to finally be on track. After a lifetime of interruptions to his education, his football career, and his plans to join the Marines, he found his way. He had launched a modeling career and appeared in ads for brands including Zumiez and Adidas. He had all but forgotten he’d ever had cancer.
Then Wright slipped on a sidewalk in 2013 and heard his ribs crack. He walked himself the few blocks to Seattle Children’s Hospital. The hospital was a familiar place. He had lived near it since at age 8, when he was diagnosed with leukemia. He had then spent several years there in treatment for two bouts of acute lymphoblastic leukemia (ALL), the second when he was 15.
After examining his ribs and drawing blood, the emergency nurse told Wright to follow up with hematology oncology. “That’s when I added everything up. The broken ribs, the blood samples. I realized, they think I have it again,” Wright recalls.
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 Gardner, MD, confirmed Wright’s leukemia was back, but she didn’t give him 6 months. She suggested he be the second patient to take part in her clinical trial. The first patient had no remaining signs of leukemia just 9 days after treatment began.
The treatment, called CAR T-cell therapy, re-engineers a patient’s own immune system to recognize and attack cancer cells. This July, FDA gave CAR T-cell therapy "breakthrough therapy" designation, which fast-tracks its path to FDA approval.
CAR T-cell therapy is a type of immunotherapy, a new wave of experimental and newly approved treatments that spur the immune system to fight cancer like it does other illnesses. Immunotherapy dominated talks at this year’s American Society of Clinical Oncology meeting. Some doctors and scientists are calling it the pathway to a cure. This year the FDA has approved two more immunotherapy drugs for the treatment of melanoma and chronic lymphocytic leukemia, including pembrolizumab (marketed as Keytruda), which was approved for melanoma last month.
“We are supercharging the immune system” says Lynn Schuchter, MD, chief of hematology oncology and an immunotherapy researcher at the University of Pennsylvania. “This brings a totally new dimension to attacking a cancer cell.”
Because cancer cells share traits with healthy cells, the immune system doesn’t recognize that they are abnormal. Through Gardner’s clinical trial, researchers genetically modify a person's own T-cells -- white blood cells that travel through the body looking for infections and other things -- to recognize and attack leukemia.
Fever is a sign that the T-cells are working, but if doctors can’t manage the fever, they might have to kill the T-cells with a different drug and end the cancer treatment.
After researchers re-engineered Wright’s cells in a lab, Wright got his cells back through an IV, and everyone waited for him to get a fever. Two weeks later, Wright’s fever landed him in intensive care and doctors considered killing the cells.
“I wasn’t ready for them to do that," Wright said. "I asked if we could give it another day or two.”
Two days later, Wright’s fever dropped. When he was well enough for a spinal tap to test for leukemia a few days later, the cancer was gone.
'It Really Works'
Wright, now 21, has since had a bone marrow transplant, an additional 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 Brentjens, MD, PhD, an oncologist at Memorial Sloan Kettering Cancer Center, who has spent 20 years researching ways to manipulate immune cells to fight cancer. “That’s often an indication that you’re not looking at a one-patient thing or a fluke. It really works in this disease.”
Since 2009, researchers at Sloan Kettering, the University of Pennsylvania, and the National Cancer Institute have tried this treatment on about 100 patients with ALL. More than 70 have gone into complete remission. Results like this earned the treatment its breakthrough status at the FDA.
“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 continue testing modified T-cells in patients 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. Early research in this area says the answer could be “yes."
Cutting the Brakes
In another form of immunotherapy, researchers attempt to release the brakes on the immune system. Cancer is allowed to develop in part because the immune system doesn’t attack every little thing 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 system response. Researchers now explore how to temporarily release those brakes to unleash the immune system on cancer cells without attacking the rest of the body as well.
Certain proteins on the surface of immune cells control these so-called brakes. The drugs that cut the brakes are man-made antibodies that shut down one or another of those proteins. But it's risky: The immune system could attack normal cells, too. This can result in 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.
Other man-made antibodies target different steps in cancer growth and progress.
Some patients with advanced metastatic melanoma, the most deadly skin cancer, go into complete remission after treatment with one of these brake-cutting drugs, such as ipilimumab, marketed as Yervoy.
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, his liver, and his brain. He soon had lumps in his back and under his arm that could be felt. Before his last round of chemotherapy at Cancer Treatment Centers of America at 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 Sasura might respond. 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 says.
Sasura finished the treatment -- four infusions over 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 that these results can be repeated with other cancers. Clinical trials with ipilimumab include patients with cancers of the breast, lungs, cervix, prostate, head and neck, pancreas, kidneys, and blood.
A year or more after immunotherapy, people like Sasura and Wright no longer consider 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 go back to the gym months before most transplant recipients. Back in shape, he wants to return to modeling.
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.”
“I feel like this treatment worked,” Wright says. “I feel I am truly done with this.”