Children's Mercy Helps Break Ground with Historic Treatment of Pediatric Cancer

Renae Proskovec of Omaha was running out of options when she came to Children’s Mercy in March for a revolutionary therapy that marked a historic moment in the treatment of pediatric cancer.

The 13-year-old with leukemia had been in remission for 10 years before she experienced a relapse. Her disease was difficult to treat, was complicated by the fact that she has Down Syndrome, and she wasn’t responding well to chemotherapy.

“Renae’s parents were faced with some difficult decisions about what treatment to pursue next,” said Doug Myers, MD, Hematology/Oncology/BMT. Options included bone marrow transplant, or a groundbreaking treatment just approved by the FDA in August 2017 known as “Kymriah.”

The family chose Kymriah, which in simple terms means white blood cells (T-cells, the body’s natural defenders) in Renae’s own immune system were reprogrammed to detect and destroy cancer cells. The treatment uses Chimeric Antigen Receptor technology (CAR T for short), where T-cells are re-engineered to target specific proteins on the surface of cancer cells.

Children’s Mercy has a proud history in the development of CAR T therapies for children and young adults. The hospital supported early development of the technology and its experience dates back to 2010 when Children's Mercy was one of only a few institutions with open clinical trials of CAR technology.

Because of the success in early clinical trials targeting CD19, a surface protein on a particular type of leukemia cells and the surface of normal B-cells, pharmaceutical companies became interested in developing the therapy. Children's Mercy's experience in CAR technology made the hospital an attractive site for the multi-site trial of this revolutionary treatment. Children's Mercy entered into an agreement with the health care company Novartis, participated in the Novartis trial of Kymriah (the product developed by Novartis) and the commercial Novartis treatment available here was the first FDA-approved CAR treatment for cancer anywhere.

The process

Renae’s T-cells were collected at Children's Mercy and sent to Novartis for processing, which takes about 22 days. She received low-dose, low-toxicity chemotherapy to hold her leukemia in check while the genetically modified Kymriah cells were being prepared.

Renae’s Kymriah Infusion was done in March as an outpatient procedure; the Kymriah product (which amounts to a couple of tablespoons in volume) was injected back into her body.

“Most people are surprised at how uneventful the infusion is,” said Sarah Pearson, RN, BSN, CPN, Program Manager, BMT/Cellular Therapy, Hem/Onc/BMT. “She slept through the entire procedure.”

Renae spent two nights in the hospital later in the week following the infusion and experienced a low-grade fever (an expected outcome of the treatment), stayed in the Kansas City area for several weeks for monitoring, then returned home to Omaha.

Dr. Myers explained that Renae’s mild fever was the result of a side effect called Cytokine Release Syndrome (CRS), which can be the first sign of inflammation created by Kymriah attacking the leukemia cells. CRS usually occurs in the first three weeks after infusion.

“It may stay a mild fever or progress to life-threatening complications that have to be managed by the critical care unit,” Dr. Myers said. “It can make patients feel extremely ill, but once resolved, many patients feel completely back to normal.”

Renae was lucky to experience only a mild case of the side effect.

“She’s done beautifully,” Dr. Myers said. “Since her discharge, she says she’s felt as well as she’s ever felt. Her mother said in the past there may have been times when she thought she felt well, but she never really knew how bad she was because she’s never felt this well before.” Dr. Myers attributes that to the low toxicity of Kymriah Infusion compared to traditional chemotherapy.

“I think it speaks to how well patients feel when they get away from all the toxic therapies and are treated with approaches that are more natural.”

Sarah said, “When we use normal chemotherapy it kills the good cells and the bad cells; this way we minimize the killing of good cells because the treatment is targeted at cancer cells.”

So far, so good

Although Renae is in remission, “The perspective on this is that it’s not considered a cure at this point,” Dr. Myers said. “But this therapy has provided prolonged remission in clinical trials for a large number of patients who had no other option. There are few other options that would provide this potential for long-term remission. The first child treated in the clinical trial is now over six years out from treatment without relapse, and in our clinical trials at Children’s Mercy we’ve had patients in remission for over three years.”

An article in the “New England Journal of Medicine” that Dr. Myers co-authored said that about 50 percent of patients treated and don’t receive any other therapy will still be in remission a year later. The remission rate was 90 percent at one month; at six months, remission rates drop into the 70 percent range; and at one year it is about 50 percent.

“But that’s much better than anything else that was out there,” Dr. Myers said. “There really has never been a treatment for patients with this poor a prognosis that has accomplished that kind of efficacy in treatment response.”

The future: for patients and Children's Mercy

Since Renae’s case, Children's Mercy has performed Kymriah Infusion for several other patients, and as a treatment center the hospital is receiving an increasing number of inquiries and referrals.

“So many patients are seeking this out as a form of treatment because other treatments have failed to cure them,” Dr. Myers said.

“We originally thought we would do about five a year, and we’re well on track for that,” Sarah said.

Kymriah Infusion treatment is limited to a high-risk population of leukemia patients who have relapsed at least once and have very few, if any other treatment options, but learnings from such CAR technologies hopefully will expand treatment to other conditions.

Being a treatment center is important for Children's Mercy because, “Patients who find themselves in a situation where standard therapies have not been adequate don’t have to travel elsewhere for this particular therapy,” Dr. Myers said. Patients need to stay near the hospital for one month and then in close follow-up after that. Having the treatment center in the region keeps families close to home.

“This also speaks about the ability of our institution to handle complex gene-transfer studies,” Dr. Myers said. “It helps with our name recognition and also promotes expanding research in this area, not just CAR T, but with other immunotherapies. It means more groundbreaking treatments can have their origin here.”

Learn more about the Cancer Center at Children's Mercy.

Learn more about Experimental Therapeutics in Pediatric Cancer.