Chimeric antigen receptor (CAR) T-cell (CAR-T) therapies have shown high remission rates in patients with B-cell precursor acute lymphoblastic leukemia (ALL) and B-cell lymphomas, but longer follow-up has revealed that durable remissions are lacking. Approximately 30% to 50% of patients who achieve disease remission at 1 month with CD19 CAR-T eventually relapse, usually within 1 year of treatment.

“That’s the big problem,” said Terry Fry, MD, department of pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, during an interview with Cancer Therapy Advisor. Dr Fry coauthored a review article in Nature with Nirali Shah, MD, from the pediatric oncology branch of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), in Bethesda, Maryland, in which he detailed the barriers preventing CAR-T therapies from reaching their full potential.1

The review article featured an exhaustive list of barriers, including cost and insurance coverage to promote patient access; manufacturing of a high-quality, effective CAR-T therapies, and the optimal management of toxicity (done in such a way that would not compromise efficacy). Additionally, the review authors underscored the need for reliable and uniform criteria to define the toxicity and potency of any CAR-based product.

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Currently, the most prominent barrier to the success of CAR-T is likely disease relapse, and generally, there are 2 possible explanations for cancer recurrence following treatment with CAR-T.

The first reason is the poor persistence of CAR-T cells after infusion, and improvement strategies will likely involve the optimization of manufacturing and design of the CAR-T product, as well as gaining a deeper understanding of T-cell biology and CAR-T cell function.

In addition, alternative strategies for CAR-T administration are under way. For example, Seattle Children’s Hospital, Washington, is conducting a pilot study (ClinicalTrials.gov Identifier: NCT03186118) to determine whether administering T-cell-antigen–presenting cells (T-APCs) after CD19 CAR-T therapy could improve persistence and reduce disease relapse.