Developing CAR T Cells for Children and Adolescents with Cancer

Given the breakthroughs in the use of chimeric antigen receptor (CAR) T cell therapy for the treatment of hematological malignancies in adults, there is great interest in the development of these treatments that are safe and effective for cancer in patients who are children and adolescents.

The seventh Paediatric Strategy Forum, held earlier this year and sponsored by ACCELERATE in collaboration with the European Medicines Agency and the U.S. Food and Drug Administration, focused on the development of CAR T cells for children and adolescents with cancer. The goals of the forum were to review the current CAR T landscape and identify future opportunities and current challenges to the development of this treatment for younger patients with cancer. Details of the Forum were published in the European Journal of Cancer.

“The development of CAR T-cells for patients with hematological malignancies, especially B cell precursor acute lymphoblastic leukemia (BCP-ALL), has been spectacular. However, currently, there are scientific, clinical and logistical challenges for use of CAR T-cells in BCP-ALL and other pediatric malignancies, particularly in acute myeloid leukemia (AML), lymphomas, and solid tumors,” wrote the authors of the report.  

One of the studies discussed was ELIANA, which evaluated tisagenlecleucel, an autologous CD19-targeted CAR T, in children and adolescents or young adults (AYAs) with relapsed/refractory BCP-ALL. In this trial, the complete repone (CR) rate to the CAR T cells was 81%, with a 59% probability of relapse-free survival (RFS) at 12 months. 

“Seventy-nine of 92 patients enrolled had CAR T-cells infused, highlighting critical factors of cell manufacturing difficulties or leukemia progression and clinical instability that precluded infusion,” the report authors noted. “Although the response is of limited durability in about half of the patients, other academic pediatric and adult studies of autologous CD19 CAR T-cell therapy products have confirmed their high initial response rates.”

The forum also focused on the prospect of CAR T cell treatment as first- or second-line therapy in high-risk patients who may relapse on conventional therapies.

“Identifying patients with very early and early relapse in whom CAR T-cell therapy may replace hematopoietic stem cell transplantation and be definitive therapy versus those in whom it provides a more effective bridge to hematopoietic stem cell transplantation is a very high priority,” the authors commented. “Development of approaches to improve persistence, either by improving T cell fitness or using more humanized/fully humanized products and co-targeting of multiple antigens to prevent antigen escape, could potentially further optimize therapy.”