4CPS-216 Case series: real-world effectiveness and safety of tisagenlecleucel for the treatment of B-cell precursor acute lymphoblastic leukaemia in paediatrics

<h3>Background and Importance</h3> Tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of B-cell precursor acute lymphoblastic leukaemia (ALL) that is refractory or in relapse. <h3>Aim and Objectives</h3> To analyse the effectiveness and safety of tisagenlecleucel in paediatric patients with B-ALL. <h3>Material and Methods</h3> Retrospective observational study of all patients with B-ALL treated with tisagenlecleucel in our centre. Study period: August 2019 to September 2024. Variables collected: demographic (age, sex), clinical (diagnosis), therapeutic (previous treatments), effectiveness (overall remission rate (ORR): proportion of patients in complete remission (CR) or complete remission with incomplete blood count recovery (CRi) with minimal residual disease (MRD) &lt;0.01% at 28 days, 3, 6 and 12 months, and median overall survival (mOS)), safety (cytokine release syndrome (CLS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, infections, macrophage activation syndrome (MAS) and hypogammaglobulinaemia). <h3>Results</h3> Eight patients, 62.5% male, median age 6 years (3–15). 75% with previous allogeneic haematological transplant and one received blinatumomab. 100% were in relapse pre-CART receiving bridging therapy. Pre-CART tumour load: 49.40% (0.01–96.00). Median follow-up: 12.36 months (3.0–41.4). Effectiveness: ORR at 28 days 87.5%, at 3 months 62.5%, at 6 months 37.5%, at 12 months 14%. 83.3% relapses CD19-. mOS= 11.5 months (3.0–14.7). <h3>Safety</h3> CRS: 100% of patients at 1.5 days(0–6) (25% grade ≥3), 50% needed tocilizumab and 25% tocilizumab+corticosteroids. 62.5% admitted to ICU. ICANS: 37.5% at 10 days (9–11) (66.7% grade ≥3). Infections: 37.5%. Cytopenias: 100% (37.5% grade ≥3). MAS: 50%. Hypogammaglobulinaemia: 100%, all needed immunoglobulins. At the end of follow-up three patients were still alive, one after 42 months in CR. The rest died due to progression B-ALL. <h3>Conclusion and Relevance</h3> Tisagenlecleucel effectiveness in our cohort was lower than that observed in the pivotal clinical trial, while maintaining a similar safety level. The majority of relapses are CD19 negative. More detailed analysis of factors that could influence response is needed, as well as a larger sample size in order to identify optimisation strategies, ensure maximum benefit from this therapy and obtain conclusive results. <h3>References and/or Acknowledgements</h3> Maude SL, Laetsch TW, Buechner J, <i>et al</i>. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukaemia. <i>N Engl J Med</i>. 2018;<b>378</b>(5):439–448. doi:10.1056/NEJMoa1709866 <h3>Conflict of Interest</h3> No conflict of interest