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

Tis-cel is already approved by the United States Food and Drug Administration for the treatment of pediatric relapsed/refractory B-ALL, but 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 She added that, “This data has direct clinical applicability, as it supports use of higher dosing, as available, within the approved tisagenlecleucel dose range.”

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The multicenter, retrospective study evaluated data from 180 pediatric patients with relapsed/refractory B-ALL from the Pediatric Real World CAR Consortium who received commercial tis-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 was administered, with the dose ranging from quartiles of 0.134-1.300 x 106 to 2.401-5.100 x 106 CAR-T cells/kg.

Higher doses of tis-cel was significantly associated with improved outcomes.  The overall 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), 0.4 (95% CI, 0.22-0.73), and 0.24 (95% CI, 0.12-0.49) in the 1.3 to 1.7, 1.7 to 2.4, and 2.4 to 5.1 x 106 dose groups, respectively, compared with the lowest dose group (P <.001).

Patients who received higher doses of tis-cel were more likely to remain in remission, with a significant improvement in relapse-free survival with higher doses (P =.002). At 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 dose groups, ranging from 83% to 92% (P =.2).

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

The authors concluded that these data “indicate that higher tis-cel doses associated with superior survival outcomes in the real-world setting and suggest further exploration of higher dosing strategies, within the safe range of tis-cel, in the clinical setting.”

Disclosures: Some of the 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.