Tisagenlecleucel Shows Promise in Pediatric Patients with ALL

The CAR T-cell therapy tisagenlecleucel showed promising anti-tumor 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 The Lancet Hematology.1

In an international, multicenter, retrospective cohort study, conducted at 15 hospitals across ten countries in Europe, researchers found that after a median follow-up of 14 months of previously treated patients given tisagenlecleucel overall survival (OS) was 84% (n = 64–93; 5 patients had died), event-free survival (EFS) was 69% (47–83; 9 events), and stringent EFS was 41% (23–58; 18 events). Moreover, 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 pre-treatment 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 comprehensively reported cohort of younger children treated with licensed CD19-targeting 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 a hematological recovery. All responses were reached by 30 days after the tisagenlecleucel infusion and had been associated with measurable residual disease negativity. Moreover, 7 patients received their infusion after attaining a measurable residual disease-negative bone marrow status after their bridging therapy and without measurable extramedullary disease. Of the 4 patients who did not have a response died of disease progression within 3 months after their infusion.

OS at 6 months in this group was 88% (95% CI, 71%–95%) and at 12 months 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 months and 12 months, but in comparison, stringent EFS was 83% at 6 months and 67% at 12 months.

Of the 31 patients who received a complete response 8 patients had a disease relapse during follow-up with 2 relapses involving evolution to CD19-negative disease, while one patient had a mixture of CD19-positive and CD19-negative blasts on biopsy of an extramedullary chloroma. However, there were no cases of lineage switch as a cause for emergence of CD-19-negative disease in patients given a tisagenlecleucel infusion, and the other 5 relapses were CD19-postive still.

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

The median age of the entire 38-patient cohort was 5.2 months and at the time of tisagenlecleucel infusion the median age was 17 months. Eighty-two percent of patients had been previously treated according to the Interfant-06 protocol and 76% had KMT2A-rearranged ALL. Most patients received previous immunotherapy with 18% receiving previous inotuzumab ozogamicin and 37% had received blinatumomab.

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

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

Grades 1 or 2 neurotoxicity, or immune effector cell-associated neurotoxicity syndrome, in patients given tisagenlecleucel was seen in 26% of patients, and prolonged cytopenia was observed in 15 patients. Infections were seen in ten of the evaluable patients with most being grade 3 or worse, with 2 cases of febrile neutropenia, but there were no deaths due to toxicity.

“Our findings are encouraging with respect to the historical outcomes of infant acute lymphoblastic leukaemia following HSCT, and, if confirmed with longer follow-up, they 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 leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study. Lancet Haematol. 2022 Oct;9(10):e766-e775. doi: 10.1016/S2352-3026(22)00225-3

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