Exploring The Roles of CAR T Cells in Pediatric Hematologic Malignancies

In a cobranded episode between Oncology On the Go, hosted by CancerNetwork^®, and the American Society for Transplantation and Cellular Therapy’s (ASTCT) program ASTCT Talks, Terri Lynn Shigle, PharmD, and Vinita Pai, PharmD, MS, BCPPS, spoke about the use of CAR T-cell therapy for pediatric populations with hematologic malignancies. Their discussion explored how real-world data compare with clinical trial findings, strategies for mitigating toxicities in pediatric patients, considerations for ensuring long-term survivorship, and other key areas.

The hosts began with an overview of how far the cellular therapy field has progressed since the FDA approval of tisagenlecleucel (tisa-cel; Kymriah) for patients up to 25 years old with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory in second or later relapse in August 2017.Despite the availability of several cell therapy products in the modern oncologic field, however, tisa-cel remains the primary FDA-approved option for pediatric patients, illustrating a gap in pediatric-specific care.

Pai highlighted several factors associated with response to CAR T therapy, including prior nonresponse to blinatumomab, the number of prior therapies, bone marrow disease burden, active extramedullary disease at infusion, and adequate fludarabine exposure during lymphodepleting chemotherapy. Furthermore, the hosts discussed how logistical hurdles like financial burden and proximity to cell therapy centers represent barriers to treatment for pediatric and adult patients alike, although catheter placement during leukapheresis serves as a unique challenge when treating younger populations.

According to Pai, future initiatives in the field may include investigating more optimal timing of leukapheresis for pediatric populations and determining the right time for transplant depending on a patient’s extent of relapse. She also discussed emerging strategies, including dual-antigen CAR-T cells, natural killer cell therapies, and off-the-shelf allogeneic CAR T cells, which warrant further investigation.

Shigle is a clinical pharmacy specialist in the Stem Cell Transplantation & Cellular Therapy Department at The University of Texas MD Anderson Cancer Center. Pai is an associate clinical professor in the Division of Pharmacy Practice and Science at The Ohio State University.

Reference

O'Leary MC, Lu X, Huang Y, et al. FDA approval summary: tisagenlecleucel for treatment of patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Clin Cancer Res. 2019;25(4):1142-1146. doi:10.1158/1078-0432.CCR-18-2035