CAR T-Cell Treatment at Higher Doses Reveal Beneficial Survival Data Without Worry of Added Toxicity

Tisagenlecleucel boosted survival rates in children with B-cell lymphoblastic leukemia. Further research will be planned to examine the data and analyze additional clinical variables.

Higher doses of tisagenlecleucel (Kymriah), a chimeric antigen receptor (CAR) T-cell therapy, displayed better survival rates at 1 year for young patients compared with patients who received lower doses who have B-cell lymphoblastic leukemia (B-ALL). Doses remained within the FDA-approved dosing range.1

“In the past, we did not have data to guide clinical decisions around commercial CAR T-cell dosing and didn’t know if higher doses would affect toxicity and compromise outcomes, or support enhanced anti-leukemia effect,” said Liora Schultz, MD, pediatric oncologist at the Stanford Children's Health, Lucile Packard Children's Hospital, and the study’s lead author. “This data has direct clinical applicability, as it supports use of higher dosing, as available, within the approved tisagenlecleucel dose range.”

ALL has been found to be the most common type of childhood cancer, with B-ALL being the most common subtype of the disease. Chemotherapy often suffices to treat B-ALL, but approximately 20% of patients either do not respond to chemotherapy or relapse after. In response, CAR T-cell therapy is growing to become a pivotal component for standard of care as an alternate or supplement therapy to stem cell transplantation for young patients with relapsed or refractory B-ALL

For patients weighing 50 kg or less, the approved dosing range is 0.2 to 5 × 106 CAR T cells/kg. For patients weighing over 50 kg, the approved dosing range is 10 to 250 × 106 CAR T cells/kg. CAR T cell numbers vary for each patient considerably, based on the number of CAR T cells obtained initially and at what rate the modified cells grow in the laboratory.

Investigators analyzed 185 patients aged 26 or younger who received tisagenlecleucel for relapsed or refractory B-ALL for overall survival, event-free survival, and relapse-free survival after 1 year. Patients receiving the higher dose range (2.4-5.1 × 106 cells/kg) had higher survival rates across those 3 end points vs patients who received treatment at the lower dose range (0-1.3 × 106 cells/kg). Eighty-six percent of patients in the higher dose group were alive at the end of 1 year vs 59% who were still alive in the low dose group. Investigators did not find any evidence of increased toxicity or safety concerns with the higher treatment dose range.

Such results suggest higher doses of tisagenlecleucel can achieve more effective response without increased toxicity risk.

“A lot of effort is focused on complex engineering and development of next-generation CAR-T therapies,” said Schultz. “This study aims to explore if clinical manipulations using our current approved construct, tisagenlecleucel, can achieve even incremental advances in the field.”

Further research will be planned to examine the data and analyze additional clinical variables, which may influence results after CAR T-cell therapy.


Higher doses of CAR-T therapy bring survival advantage for young patients with hard-to-treat B-ALL. Press release. American Society of Hematology; August 8, 2022. Accessed August 10, 2022.