Higher doses of tisagenlecleucel (tisa-cel) improved survival outcomes among pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) without increasing toxicity, according to a retrospective study published in Blood Advances.1

Tisa-cel is already approved by the US Food and Drug Administration for the treatment of pediatric relapsed/refractory B-ALL, but it is administered as a single infusion with a wide dose range. The aim of this study was to determine if cell dose affects survival outcomes and remission.

“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,” Liora Schultz, MD, of Stanford’s Children Health and Lucile Packard Children’s Hospital, and lead author of the study, said in a press release.2 “This data has direct clinical applicability, as it supports use of higher dosing, as available, within the approved tisagenlecleucel dose range.”

Continue Reading

The multicenter, retrospective study included data from 180 pediatric patients with relapsed/refractory B-ALL from the Pediatric Real World CAR Consortium who received commercial tisa-cel.1 Patients were classified according to cell dose received, and outcomes were evaluated.

A median of 1.7 x 106 CAR-T cells/kg were administered, with the dose quartiles ranging from 0.134-1.300 x 106 to 2.401-5.100 x 106 CAR-T cells/kg.

Higher doses of tisa-cel were significantly associated with improved outcomes. The 3-year overall survival (OS) was 58.9%. Compared with the lowest dose quartile, higher doses incrementally improved OS (P =.008), with a hazard ratio (HR) of 0.7 (95% CI, 0.34-1.45) for the 1.3-1.7 x 106 dose group, 0.4 (95% CI, 0.18-0.87) in the 1.7 to 2.4 x 106 dose group, and 0.22 (95% CI, 0.08-0.61) in the highest dose group of 2.4 to 5.1 x 106.

Event-free survival was also improved with higher doses, with HRs of 0.51 (95% CI, 0.29-0.88) for the 1.3-1.7 x 106 dose group, 0.4 (95% CI, 0.22-0.73) for the 1.7 to 2.4 x 106 dose group, and 0.24 (95% CI, 0.12-0.49) for the 2.4 to 5.1 x 106 dose group, compared with the lowest dose group (P <.001).

Patients who received higher doses of tisa-cel were more likely to remain in remission, with a significant improvement in relapse-free survival with higher doses (P =.002). In the 1.3 to 1.7 dose group, the HR was 0.4 (95% CI, 0.19-0.82), followed by 0.43 (95% CI, 0.2-0.89) in the 1.7 to 2.4 dose group, and 0.18 (95% CI, 0.07-0.49) in the highest dose group. Response rates were similar across the groups, ranging from 83% to 92% (P =.2).

Rates of cytokine release syndrome (CRS) were similar across the dose groups, ranging from 52% to 65% (P =.2). Rates of neurotoxicity were similar as well, ranging from 16% to 26% (P >.9). There was no difference in rates of grade 3 or higher CRS or neurotoxicity or the need for treatment with steroids or tocilizumab.

These data suggest that higher tisa-cel doses are associated with superior survival outcomes in the real-world setting and suggest a need for further exploration of higher dosing strategies, within the safe range, in the clinical setting, according to the researchers.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Stefanski H, Eaton A, Baggott C, et al. Higher doses of CAR-T therapy bring survival advantage for young patients with hard-to-treat B-ALL. Blood Adv. Published online August 8, 2022. doi: 10.1182/bloodadvances.2022007246
  2. Higher doses of CAR-T therapy bring survival advantage for young patients with hard-to-treat B-ALL. News release. American Society of Hematology. August 8, 2022. Accessed August 10, 2022. https://www.hematology.org/newsroom/press-releases/2022/higher-doses-of-car-t-therapy-bring-survival-advantage.

This article originally appeared on Hematology Advisor