LOS ANGELES–(BUSINESS WIRE)–The U.S. Food and Drug Administration has approved a novel cancer
treatment that resulted in 83% of patients with resistant leukemia going
into remission, and the majority remaining cancer free after a year. The
approach is called CAR-T therapy, and it uses a patient’s own white
blood cells that have been genetically re-engineered to specifically
target and kill cancer cells. The newly licensed therapy, called
Kymriah, is produced by Novartis and has been approved to treat children
and young adults with relapsed acute lymphoblastic leukemia.
“Despite the nearly continuous advances that have been made in the
treatment of leukemia, this malignancy remains a leading cause of death
in childhood,” says Alan Wayne, MD, director of the Children’s Center
for Cancer and Blood Diseases at Children’s Hospital Los Angeles and
professor of Pediatrics and Medicine at the Keck School of Medicine of
the University of Southern California. “At CHLA, we can now offer potent
immunotherapies, like CAR-T, to children with the most resistant
Children’s Hospital Los Angeles was one of a small number of sites that
participated in the trial that led the FDA to approve Kymriah, and it is
one of 32 hospitals in the U.S. that have been approved to treat
patients with this therapy.
At CHLA, the Novartis CAR-T trial is being led by Michael Pulsipher, MD,
section head of Blood and Marrow Transplantation. He and Wayne are
leading a number of other CAR-T studies to determine the effectiveness
of the treatment in different types of patients.
Treatment with CAR-T
Ninety percent of children diagnosed with acute lymphoblastic leukemia
are cured. However, of those who relapse, only a minority survive
long-term. So when Alexis Bonilla was 11 years old and his disease
returned for the third time, his doctor immediately referred him to CHLA.
“I told Alexis’ parents that the good news is we have a new therapy, and
after being treated with it, your son has nearly a 90 percent chance of
remission,” says Pulsipher. “The not-so-good news is that it might
initially make him very sick.” Pulsipher told the couple about a
clinical trial for chimeric antigen receptor T cell (CAR-T)
Alexis’ mom, Daysi Bonilla, and his stepdad, Jorge, agreed right away to
have their son in the study.
T cells are a type of white blood cell that is part of our defense
against viruses, bacteria and to a lesser extent, cancer. CAR-T therapy
harnesses the immune system by engineering the T cells to specifically
attack cancer cells. The opposite of a “one size fits all” strategy,
this treatment is individually created for each patient using his or her
A sample of Alexis’ blood was taken and sent to the lab so that his T
cells could be genetically engineered to produce a chimeric antigen
receptor (CAR) on their surface. The receptor directs the T cells to a
protein, called CD19, present on leukemia cells. When the CAR-T cell
connects with the CD19 protein, the leukemia cell is destroyed.
Alexis received several weeks of high-dose chemotherapy to kill as many
leukemia cells as possible. Then his modified T cells were re-infused.
Waiting to see what happens
“Ninety percent of patients develop a fever after the cells are
infused,” says Pulsipher. “It’s a side effect that we want to see
because it indicates that the CAR-T cells are functioning appropriately.”
He explains that the greater number of tumor cells a patient has, the
greater their immune response. Sometimes, the battle between the
supercharged T cells and the large number of cancer cells becomes
extreme, causing the patient’s blood pressure to plummet.
This reaction, known as cytokine release syndrome, or “cytokine storm,”
occurred in Alexis. He was moved to the intensive care unit so that his
response could be safely managed. “It was scary,” says Daysi.
What’s next for CAR-T?
When an experimental therapy is introduced into the clinic at the
earliest stage of investigation, it is tested in people who have disease
that is resistant to all other treatments—basically, the sickest
“As we gain experience with CAR-T and trials are open to a wider variety
of patients, I anticipate that we will see less-severe side effects in
people with earlier-stage disease,” says Pulsipher, who is also a
professor of Pediatrics at the Keck School of Medicine of USC. Until
then, he and his colleagues are glad to have this truly life-changing
therapy to offer their most seriously ill patients.
Alexis made a rapid recovery. Two months after starting treatment at
CHLA, he was ready to return home. He always bounces back, Daysi says.
“He wants life,” adds Jorge.
Alexis has been in remission from leukemia for nearly 20 months.
Children’s Hospital Los Angeles
Ellin Kavanagh, 323-361-8505