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CAR T-Cell Therapy Approval Starts New Path in Childhood Leukemia

Angelica Welch
Published: Thursday, Nov 16, 2017

Sarah K. Tasian, MD
Sarah K. Tasian, MD
The historic FDA approval of tisagenlecleucel (Kymriah) marked the beginning of a new era of personalized medicine in hematologic malignancies, especially for select pediatric patients.

This CD19-directed chimeric antigen receptor (CAR) T-cell therapy was approved for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. This indication also signified an advance for the treatment of pediatric leukemia, a field in which drug development is slow.

Research is now being conducted with CAR T-cell therapy in pediatric acute myeloid leukemia (AML), with a possibility for a clinical trial opening over the next year.

In an interview with OncLive, Sarah K. Tasian, MD, an attending physician and assistant professor of pediatrics in the Division of Oncology at Children’s Hospital of Philadelphia, discussed the success of CAR T-cell therapy, as well as novel agents and immunotherapies that appear promising in the treatment of children with leukemia.

OncLive: What has been the impact of the recent FDA approval of tisagenlecleucel on the field of pediatric hematology?

Tasian: The approval of CD19-redirected CAR T cells for children with B-ALL is a historic landmark. Several institutions across the country, including CHOP and the University of Pennsylvania, have conducted clinical trials investigating these therapies in adults and children with B-cell ALL or lymphoma and demonstrated remarkable results. This now gives a lot of hope to patients who have highly treatment-resistant disease who can now potentially be cured. It is truly one of the most exciting developments in oncology and especially in childhood leukemia in the past 50 years.

What research related to CAR T-cell therapy have you been involved with?

I am at the Children's Hospital of Philadelphia, where the first child with B-ALL was treated with CD19 CAR T cells. Given this remarkable success, our clinical immunotherapy team has subsequently treated hundreds of children and young adults on its research trials. Through multi-institutional grant mechanisms, our group also [closely] collaborates with other pediatric institutions that have been conducting these pivotal CAR T cell trials and other laboratory-based research, such as the National Cancer Institute (NCI) and Seattle Children's Hospital. It is a very small community in that respect of talented, bright investigators focused upon developing innovative therapies together for children with high risk cancers. 

On a research level, my laboratory and collaborators are working to develop CAR T cell immunotherapies for children with AML. We have made a lot of progress in preclinical work, and several CD123 and CD33 CAR T cell trials are underway for adults with relapsed AML. We are planning to open a first-in-child CAR T cell trial in 2018 for children with relapsed or refractory AML. The success story of CD19 CAR T cell immunotherapy for ALL is very inspiring, and we would love to see similar success in pediatric AML, but it has been a much more difficult endeavour. Other CAR T cell immunotherapy strategies that we are investigating still in the preclinical phase are targeting TSLPR in ALL and FLT3 in ALL and AML. We are hoping to have trials against both of those antigens within the next 2 years.

Do you foresee any of these successes from ALL transferring to AML?

We hope so. It has certainly been a nice, simultaneous paradigm. The targets for CAR T cells in AML have been more challenging to identify, and the toxicities in patients with AML will likely be quite different and perhaps a bit scarier than what we typically experience with patients with ALL.

Is immunotherapy showing any promise in children with leukemia?

Ongoing studies are actively investigating other targets in ALL beyond CD19, particularly CD22. The NCI just published very exciting first results of its CD22 CAR T cell trial, and several pediatric institutions across the country have active phase 1 CD22 trials for children with relapsed CD22+ B-ALL.

Studies are now starting to look at targeting 2 leukemia proteins simultaneously. The NCI and Stanford Cancer Institute have a brand new trial with a CAR T-cell therapy that targets CD19 and CD22 simultaneously. The question in that trial is, “Can similar rates of remission be achieved, but also possibly prevent some tumor antigen loss that is currently seen in the CD19 or CD22 alone trials?” Antigen loss is a major mechanism of failure of these and other targeted immunotherapies, so will certainly be something for which to watch closely. 


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