SOURCES: Stephan Grupp, M.D., Ph.D., director, translational research, Center for Childhood Cancer Research, Children's Hospital of Philadelphia; Michel Sadelain, M.D., Ph.D., director, Center for Cell Engineering, Memorial-Sloan Kettering Cancer Center, New York City; Oct. 16, 2014, New England Journal of Medicine
WEDNESDAY, Oct. 15, 2014 (HealthDay News) -- An experimental immune-system therapy can often lead to complete remission in leukemia patients who have run out of other options, a new study confirms.
Researchers found that 27 of 30 children and adults with advanced acute lymphoblastic leukemia (ALL) went into full remission after receiving genetically tweaked versions of their own immune system cells.
"Ninety percent of patients who had no options left went into complete remission. That's amazing," said senior researcher Dr. Stephan Grupp, of Children's Hospital of Philadelphia and the University of Pennsylvania.
However, seven patients who went into remission did eventually suffer a relapse, according to the study.
The findings, published Oct. 16 in the New England Journal of Medicine, confirm what smaller studies have suggested: The therapy offers hope to people with ALL that has repeatedly eluded standard treatments.
But while past studies have focused on adults, this study included mostly children.
"It shows the therapy can work just as well in children with ALL, and it's great to see that," said Dr. Michel Sadelain, a researcher at Memorial-Sloan Kettering Cancer Center in New York City who worked on those earlier studies.
But, both Grupp and Sadelain said ongoing studies will have to clarify the therapy's role in treating ALL.
ALL is a cancer of the blood and bone marrow that progresses quickly. It's more common in children than adults, but while children are often cured with chemotherapy, adults have a poorer outlook, Sadelain said.
In the United States, about 6,000 people will be diagnosed with ALL this year, and just over 1,400 will die, according to the American Cancer Society (ACS). Adults will account for 80 percent of those deaths, according to the ACS.
The standard first treatment for ALL is three rounds of chemotherapy drugs, and for many patients that does beat back the cancer. Unfortunately, the disease often returns. At that point, Sadelain explained, the only hope for long-term survival is to have another round of chemotherapy that wipes out the cancer, followed by a stem cell transplant.
But when the cancer recurs, it is likely to be resistant to many chemotherapy drugs. The new therapy takes an entirely different approach -- enlisting the immune system to target specific proteins on ALL cells, according to the researchers.
Doctors take immune system T cells from a patient's blood. Then, they genetically engineer them to express so-called chimeric antigen receptors -- which allow the T cells to recognize and destroy ALL cells. The tweaked cells are infused back into the patient's blood, where they multiply. The researchers dubbed the engineered cells "hunter" cells.
Of the 30 patients treated in the current study, 27 quickly went into complete remission -- meaning they no longer had detectable cancer. Most of the group has been followed for at least six months, and for as long as two years, the researchers said. During that time, 19 remained in remission, while seven died after their cancer relapsed or progressed.
A major question now, Grupp said, is whether the cell therapy, alone, can keep ALL patients in remission.
Sadelain agreed. Right now, he said, if cell therapy leads to a full remission, patients are typically offered a stem cell transplant -- because transplants are known to boost people's long-term survival odds.
But some patients either do not want a transplant or can't have one -- because of other medical conditions, for instance. So, Sadelain said, it will be crucial to follow those patients over time, to see whether their cell therapy is enough to stave off a relapse.
In the current study, 15 of the patients with sustained remissions received no further treatment.
Grupp called that an "encouraging" sign that cell therapy could be a stand-alone treatment. "But we are not there yet," he stressed.
As for safety, Grupp said the major short-term risk is cytokine release syndrome -- which causes symptoms including persistent fever, a drop in blood pressure and difficulty breathing. All of the patients in the current trial had cytokine release syndrome soon after treatment, according to the study. No one died as a result of this therapy, however.
"Patients can get quite sick," Grupp said, "but it's a manageable side effect."
In July, the U.S. Food and Drug Administration granted the cell therapy a "breakthrough therapy" designation for advanced ALL -- which could speed the treatment through the standard regulatory review process, according to the researchers.
Drug company Novartis, which partially funded this study, has licensed the particular technology used in the current study and is doing a larger trial at multiple U.S. hospitals; Grupp and some of his co-researchers are inventors of the technology and stand to financially benefit.
Sadelain is a founder of Juno Therapeutics, which is also moving cell therapy into larger trials.
This treatment is still restricted to the research setting, but Grupp said patients with relapsed ALL can ask their doctors about the possibility of enrolling in a trial.
The American Cancer Society has more on acute lymphoblastic leukemia.