Tisagenlecleucel shows promise in pediatric patients with ALL

Tisagenlecleucel shows promise in pediatric patients with ALL

The tisagenlecleucel CAR T-cell therapy showed promising antitumor activity in pediatric patients with acute lymphoblastic leukemia.

Treatment with the CAR-T cell therapy tisagenlecleucel (Kymriah) shows promising antitumor activity in young children and infants with B-cell precursor acute lymphoblastic leukemia, according to findings published in Lancet hematology.1

In an international, multicenter, retrospective cohort study conducted in 15 hospitals in 10 countries in Europe, investigators found that after a median follow-up of 14 months of previously treated patients receiving tisagenlecleucel, overall survival (OS) was 84% (n = 64–93; 5 patients had died), event-free survival (EFS) was 69% (47–83; 9 events), and strict EFS was 41% (23–58; 18 events ). In addition, the probability of ongoing B-cell aplasia was 70% (95% CI: 46–84; 7 events) at 12 months. However, there was no significant association between pretreatment risk factors and outcome measures.

“Responses were durable in a substantial proportion of patients, with a median event-free survival of 20.3 months. To our knowledge, this is the largest and most comprehensive cohort of younger children treated with licensed CD19-targeted CAR T-cell therapy published to date, and the only study to systematically report the use of a licensed CAR T-cell therapy for this indication in this age group,” the researchers wrote.

Of the 28 patients who received an infusion and response could be assessed, 86% (n = 24) had a complete response with or without hematologic recovery. All responses were achieved 30 days after tisagenlecleucel infusion and were associated with measurable negativity of residual disease. In addition, 7 patients received their infusion after reaching a negative bone marrow status for measurable residual disease after their bridging therapy and without measurable extramedullary disease. Of the 4 patients who did not respond, they died of disease progression within 3 months after infusion.

The OS at 6 months in this group was 88% (95% CI, 71%–95%) and at 12 months it was 84% ​​(95% CI, 64%–93%) with an EFS rate of 75%. % (95% CI, 56%–87%) at 6 months and 69% (95% CI, 47%–83%) at 12 months. Of the 7 patients who received an infusion and had no measurable residual disease, EFS was 100% at 6 and 12 months, but in comparison, strict EFS was 83% at 6 months and 67% at 12 months. months.

Of the 31 patients who received a complete response, 8 patients had disease relapse during follow-up with 2 relapses progressing to CD19-negative disease, while one patient had mixed CD19-positive and CD19-negative blasts on biopsy from one patient. extramedullary tumor. chlorome. However, there were no cases of lineage switching as a cause of the onset of CD19-negative disease in patients receiving tisagenlecleucel infusion, and the other 5 relapses were still CD19-positive.

Fifteen of 35 patients received additional therapy during follow-up, but 6 patients had frank relapse due to either failure to respond to CAR T-cell therapy or early B-cell recovery at 6 months or less after infusion. Four children in the study were 1 year of age or older at the time of diagnosis, and one child had KMT2A-rearranged disease and did not receive the CAR T-cell infusion due to a manufacturing fault, while one child died due to his disease. However, the other 3 children received an infusion of tisagenlecluecel.

The median age of the entire cohort of 38 patients was 5.2 months, and at the time of tisagenlecleucel infusion, the median age was 17 months. 82% of the patients had been previously treated according to the Interfant-06 protocol and 76% had KMT2A-reorganized EVERYTHING. Most patients received prior immunotherapy: 18% received inotuzumab ozogamicin and 37% received blinatumomab.

For patients who received study drug, the median percentage of bone marrow blasts before lymphocyte depletion was 5%. Twenty percent had undetectable measurable residual disease, 29% had measurable residual disease that was detectable in up to 5% blasts, and 51% had a disease burden of 5% blasts or greater, with 7 patients having a disease of more than 50% explosions. The study included mainly male patients in 21 patients with 17 female patients.

Regarding the safety of this patient population, cytokine release syndrome (CRS) of any grade occurred in 60% (n=21) receiving a tisagenlecleucel infusion with grade 3 or worse in 5 patients. The median duration of CRS was 1.5 days in this cohort, with a median length of ICU stay of 2 days.

Grade 1 or 2 neurotoxicity, or immune effector cell-associated neurotoxicity syndrome, was observed in patients receiving tisagenlecleucel in 26% of patients, and prolonged cytopenia was observed in 15 patients. Infections were seen in 10 of the evaluable patients, most grade 3 or worse, with 2 cases of febrile neutropenia, but no deaths from toxicity.

“Our findings are encouraging regarding the historical outcomes of childhood acute lymphoblastic leukemia after HSCT and, if confirmed with longer follow-up, support the development of prospective studies to compare the efficacy of tisagenlecleucel against HSCT earlier in the course. of therapy. in this population,” the researchers concluded.


Ghorashian S, Jacoby E, De Moerloose B, et al. Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukemia in infants and children younger than 3 years at screening: an international, multicenter, retrospective cohort study. lancet hematol. October 2022; 9(10):e766-e775. doi: 10.1016/S2352-3026(22)00225-3

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