Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia
Amy Moskop1, Lauren Pommert2,3, Christina Baggott4
1Division of Hematology/Oncology/Blood and Marrow Transplantation, Department of Pediatrics, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI.
Insights
Tisagenlecleucel shows promise for infant B-cell acute lymphoblastic leukemia (B-ALL). This chimeric antigen receptor T-cell (CART) therapy demonstrated safety and efficacy in young patients, offering a new treatment option for this aggressive cancer.
Area of Science:
- Pediatric Oncology
- Immunotherapy
- Hematologic Malignancies
Background:
- Infant B-cell acute lymphoblastic leukemia (B-ALL) presents poor prognoses due to chemotherapy resistance and high relapse rates.
- Current treatment limitations necessitate novel therapeutic strategies for this vulnerable patient group.
- Children under 3 years were excluded from initial tisagenlecleucel studies, leaving a knowledge gap regarding its use in infants.
Purpose of the Study:
- To evaluate the safety and efficacy of tisagenlecleucel in infants diagnosed with B-ALL.
- To assess remission rates and long-term outcomes following CART therapy in this specific population.
- To determine the tolerability of tisagenlecleucel, including adverse events like cytokine release syndrome and neurotoxicity.
Main Methods:
- Retrospective analysis of data from the Pediatric Real-World CAR Consortium.
- Inclusion of 14 infants with B-ALL treated with tisagenlecleucel between 2017 and 2020.
- Evaluation of minimal residual disease status, remission duration, and adverse events.
Main Results:
- Sixty-four percent of patients achieved minimal residual disease-negative remission post-CART therapy.
- Fifty percent of patients maintained remission at the last follow-up.
- Patients with high disease burden (>M1 marrow) at infusion were refractory; however, the therapy was generally tolerable with limited severe cytokine release syndrome and no reported neurotoxicity.
Conclusions:
- Tisagenlecleucel is a safe and potentially effective immunotherapy for infant B-ALL.
- This study represents the largest cohort examining tisagenlecleucel in this population.
- Incorporating CART therapy offers a promising new avenue for treating this aggressive form of leukemia.
Abstract:
Infants with B-cell acute lymphoblastic leukemia (B-ALL) have poor outcomes because of chemotherapy resistance leading to high relapse rates. Tisagenlecleucel, a CD19-directed chimeric antigen receptor T-cell (CART) therapy, is US Food and Drug Administration approved for relapsed or refractory B-ALL in patients ≤25 years; however, the safety and efficacy of this therapy in young patients is largely unknown because children <3 years of age were excluded from licensing studies. We retrospectively evaluated data from the Pediatric Real-World CAR Consortium to examine outcomes of patients with infant B-ALL who received tisagenlecleucel between 2017 and 2020 (n = 14). Sixty-four percent of patients (n = 9) achieved minimal residual disease-negative remission after CART and 50% of patients remain in remission at last follow-up. All patients with high disease burden at time of CART infusion (>M1 marrow) were refractory to this therapy (n = 5). Overall, tisagenlecleucel was tolerable in this population, with only 3 patients experiencing ≥grade 3 cytokine release syndrome. No neurotoxicity was reported. This is the largest report of tisagenlecleucel use in infant B-ALL and shows that this therapy is safe and can be effective in this population. Incorporating this novel immunotherapy into the treatment of infant B-ALL offers a promising therapy for a highly aggressive leukemia.
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