In May 2010, Emily Whitehead started suffering from bruising on her legs and bleeding of her gums. Soon her symptoms became more serious, and she was rushed to the emergency room.

It wasn’t long after that the five-year old Pennsylvania native was diagnosed with standard risk pre-B acute lymphoblastic leukemia (ALL), which comes with an 85 to 90 percent chance of survival.

While Whitehead initially achieved remission with standard therapies, in 2011 she relapsed. Doctors gave her only a 30 percent chance of survival. After another relapse in 2012—shortly before a bone marrow transplant was scheduled—Whitehead was enrolled in a phase I clinical trial at Children’s Hospital of Philadelphia (CHOP) and was selected to be the first patient to receive an experimental gene therapy known as CAR-T therapy, which uses patients’ own genetically modified T-cells to fight the leukemia. The therapy worked, and she has been in remission for the past five years, the longest of any child that has received this therapy.

On Monday, September 18, The Washington Post spoke with the Whitehead family as well as doctors from CHOP and the National Cancer Institute (NIH), about the experimental gene therapy as part of the Chasing Cancer summit, an event where experts discussed the latest advances in cancer detection and treatment.

The CAR-T cell therapy —known as tisagenlecleucel (Kymriah) and brought to market Novartis Pharmaceutical’s—was approved for certain pediatric and young adult patients with a form of ALL in August of 2017, ushering in a new approach to the treatment of cancer.

CHOP Attending Physician Dr. Shannon Maude said during the summit that tisagenlecleucel is the first cancer treatment approved specifically for childhood cancer.

“Typically we do want to show that the drugs can be safely given in adults before we move into children,” Maude said. “This was really amazing that this was developed first in children and first approved in children.”

The treatment works by giving each patient a personalized treatment using their T-cells—which attack diseases in the body. The T-cells are collected and genetically modified to include a new gene that contains a specific protein that directs the T-cells to target and kill the leukemia cells.

Whitehead’s struggles and relapses through traditional treatment, including chemotherapy, before eventually becoming the first patient treated using the new therapy, highlights the need for different treatment options for those who do not response to traditional treatments.  

However, there are still challenges with CAR-T cell treatment.

There is a complication of the therapy called cytokine release syndrome, said NCI Associate Research Physician Dr. Nirali Shah, during the summit. Whitehead experienced this side effect during her treatment.

“CRS is essentially an inflammatory milieu that arises as the CAR cells go in,” she said. “The CAR cells go in, they see the leukemia, they expand and they start to grow in numbers and as that expansion is happening, there’s all of these inflammatory cytokines that are then released in the body that are causing a lot of the side effects that Emily had. 

“They can lead to low blood pressure, difficult deep breathing, needing to go to the ICU.  Some could even lead to some forms of neurotoxicity, which you may have heard about as well.”

In Whitehead’s case, the doctors discovered that tocilizumab, a rheumatoid arthritis treatment, could fight cytokine release syndrome.

“So what we learned from Emily was that they checked her blood to see if there were any of these cytokines that were elevated.  IL-6 was amongst one of those cytokines,” said Shah. “Tocilizumab is an IL-16 receptor blockade, so it actually blocks the ability of IL-6 to affect your organs and by giving that blockade medication, the IL-6 is no longer causing the problems that it was causing in her body.”

“What we learned from Emily was how to be able to deliver this product safely without causing that degree of toxicity.”

Shah explained that the therapy is still risky because many patients suffer side effects that can be managed, but require a lot of specialized care. 

According to Maude, there is still hope that the treatment can be improved to reduce risk and risk of relapse.

“We want to be able to overcome the relapses that we have seen,” she said. “We are also looking at the other form of relapse of having the T cells last.

“The goal of the therapy is that this could really be a living drug that will last in the body for months and years,” she added. “That happens in many patients but in some patients that does not happen and the T cells go away more quickly.”

She also said the treatment may eventually be able to be used for virtually any type of cancer.

According to Shah, there are many sites involved in the trials that led to the FDA approval and many are being trained on the therapy by Shah, Dr. Stephan Grupp from CHOP and Novartis Pharmaceutical’s.

She also said that while the new treatment is exciting, bone marrow transplant may still be required.

“I think it’s too early to say that it will be a replacement for bone marrow transplant because I think right now, we don’t have enough years with CAR cell therapy to know the durability,” she said. “And currently, the standard of the curative treatment for patients with multiply relapsed refractory ALL would be a transplant. 

“But we know that patients are going to relapse after transplant as well.  So I think what the future holds is either some combination where you’re able to use CAR cells as a bridge to transplant, potentially making the transplant less toxic.”