High Dose of Tisagenlecleucel Linked to Better Survival Rate for B-Cell Acute Lymphoblastic Leukemia


For pediatric patients with B-cell acute lymphoblastic leukemia, higher doses of tisagenlecleucel increased their rate of survival after 1 year by nearly 30%.

Young patients with B-cell acute lymphoblastic leukemia (B-ALL) who received higher doses of tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy, within the FDA-approved range experienced a significantly higher 1-year survival rate compared to patients who received lower doses, according to a study published in Blood Advances.

“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 study lead author Liora Schultz, MD, a pediatric oncologist at the Stanford Children's Health Lucile Packard Children's Hospital, in a press release.

Tisagenlecleucel was the first approved gene therapy available in the United States. Since 2017, it has treated pediatric patients with B-ALL who did not respond to chemotherapy or who experienced recurrence after being treated.

ALL is the most common cancer in children and B-ALL is the most common subtype. Although treatable with chemotherapy, approximately 20% of patients do not respond to the treatment or they relapse.

CAR T-cell therapy removes a patient’s infection-fighting T cells and genetically modifies them to identify cancer cells before reinserting them back into the body to destroy cancerous cells.

CAR T-cell therapy is a standard treatment for pediatric patients with relapsed or refractory B-ALL. It serves as an alternative or supplement to stem cell transplantation. Tisagenlecleucel is approved at 0.2-5 million CAR T cells/kg for patients who are 50 kg or less and approved at 10-250 million CAR T cells/kg for patients over 50 kg.

Physicians are still unsure of the correct dosing for this therapy. There is little evidence to determine whether higher or lower doses offer better treatment, according to the study authors. Physicians decide whether to use a higher or lower number of cells, usually based on the number of T cells obtained from the patient. Clinical trials guide dosing amounts, but such a wide range could be fine-tuned to inform decision-making going forward.

For this study, researchers analyzed 185 patients who had relapsed or refractory B-ALL. The participants, all 26 years of age and younger, were administered different doses of tisagenlecleucel for 1 year.

During that time, researchers analyzed the rate of overall survival, event-free survival, and relapse-free survival, observing that participants administered higher doses within the approved range (2.4-5.1 million cells/kg) had significantly higher survival rates than those who received a lower dose (0-1.3 million cells/kg).

Among the participants, 86% administered a higher dose of tisagenlecleucel lived until the end of the year. This was nearly 30% more than the low-dose participants, of whom 59% lived through the year. Risk of toxicity or safety concern did not increase with dose.

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


Higher doses of CAR-T therapy bring survival advantage for young patients with hard-to-treat B-ALL. EurekAlert! Aug 8, 2022. Accessed Aug 9, 2022. https://www.eurekalert.org/news-releases/960817

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