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Real-World Data Support Licensed Use of Tisagenlecleucel in Infants, Young Children With B-Cell ALL

November 21, 2022

December 2022

Leah Lawrence

Leah Lawrence is a freelance health writer and editor based in Delaware.

The safety and efficacy of chimeric antigen receptor (CAR) T-cell therapy with tisagenlecleucel in infants and children younger than 3 with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) was consistent with that seen in older children and young adults, according to study results published in Lancet Haematology.1

“Tisagenlecleucel is approved [in ALL] on the basis of the pivotal ELIANA trial that excluded children aged less than 3,” explained study author André Baruchel, MD, of Hôpital Universitaire Robert-Debré in Paris. “Despite that, the marketing authorization given by the [U.S. Food and Drug Administration] and [European Medicines Agency] is from age 0 to 25.”

Therefore, Dr. Baruchel and colleagues used real-world data to assess the feasibility and activity of tisagenlecleucel in infants and children younger than 3. The international, multicenter, retrospective study used data from 38 patients screened at 15 hospitals across 10 countries.

All eligible patients were younger than age 3 at screening and had relapsed or refractory B-cell precursor ALL. Of the 38 patients screened, manufacturing feasibility was excellent, with 35 of 38 receiving a single tisagenlecleucel infusion. About three-quarters of patients (76%) had KMT2A-rearranged ALL, a gene rearrangement that often confers chemotherapy resistance, and 66% had disease relapse after prior allogeneic hematopoietic cell transplantation (alloHCT).

With a median follow-up of 14 months, the 12-month overall survival (OS) was 94% and 12-month event-free survival (EFS) was 69%.

Dr. Baruchel said it is difficult to compare these outcomes to historical treatment of these patients because data of this advanced phase of disease in this age group are not easily available. However, as a comparison, patients with KMT2A-rearranged ALL typically have a very dismal prognosis, he said, with an EFS and OS of less than 30%.

Dr. Baruchel and colleagues also looked at an outcome of stringent event-free survival (sEFS). This was identical to the EFS definition in the ELIANA trial but incorporated measurable residual disease emergence after reaching complete response with or without hematologic recovery and receipt of further anti-leukemia therapy, including alloHCT. The 12-month sEFS was 41%.

Grade 3 or higher adverse events occurred in 14% of patients. Neurotoxicity, none of which was severe, occurred in 26% of patients. Cytokine release syndrome (CRS) of any grade occurred in 60% of patients, with severe CRS observed in 14%. The researchers wrote, “these toxicity data are reassuring for clinicians treating children in a younger age range.”

Among the study’s limitations are its retrospective nature, small cohort size, and the possibility of self-selection bias because data were contributed by centers on a voluntary basis.

Alongside the study, an editorial was published by Haneen Shalabi, DO, and Nirali N. Shah, MD, of the National Cancer Institute. They cited data from the U.S. Pediatric Real World CAR Consortium (PRWCC) of 14 patients with infant ALL (1 year of age or younger) who received tisagenlecleucel. They wrote, “although CAR T cells showed a substantial benefit in this patient group, there remains an opportunity to further optimize this therapeutic approach.”2

Understanding how CAR T cells would perform earlier in the treatment course, potentially to spare the youngest children from additional intensive or ineffective therapies, needs further exploration. 

Despite that, they wrote, “the use of [sEFS] as a CAR T-cell outcome metric to capture clinically relevant outcomes is to be commended and should be more broadly applied. The study by Ghorashian and colleagues shows feasibility, safety, and impressive response rates with tisagenlecleucel among patients with a highly aggressive subgroup of leukemia, and adds to the sparse body of literature on CAR T cells as salvage therapy for infant [ALL].”

Any conflicts of interest declared by the authors can be found in the original article.


  1. Ghorashian S, Jacoby E, De Moerloose B, et al. Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study. Lancet Haematol. 2022;9(10):E766-E775.
  2. Shalabi H, Shah NN. CD19 CAR T cells for infants and young children. Lancet Haematol. 2022;9(10):e712-e714.




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