Outcomes of Children and Young Adults with Acute Lymphoblastic Leukaemia Administered Inotuzumab Pre CAR-T Therapy

Introduction: Immunotherapies like Inotuzumab ozogamicin (InO), Blinatumomab and Chimeric antigen receptor T cell therapy (CAR-T) have revolutionized outcomes in patients with Relapse/Refractory Acute Lymphoblastic Leukaemia (R/R ALL) with event free survival (EFS) of 50% at 1 year (Maude et al. 2018). Optimal phasing of these agents has not been clearly defined and depends on antigen expression on blasts, CNS status, T cell number and prior disease response. InO, a CD22 targeting antibody-drug conjugate has proven efficacy in adults (Kantarjian et al., 2016) and children as a bridge to allogeneic stem cell transplantation (allo-SCT) with a favourable toxicity profile (Brivio et al. 2021). However, outcomes following the use of InO prior to CAR-T therapy are still not established. This study provides a retrospective analysis of children and young adults who received InO as part of pre-CAR-T management (before leucapheresis or as bridging therapy to CAR-T infusion). Methods: Patients aged 0-25years with R/R ALL were eligible for the study if they received InO pre-CAR-T therapy. Retrospective data collection was performed using a standardised form from CAR-T centres in the UK. Response to CAR-T therapy and/or relapse was evaluated at 1, 3, 6, 12 months or at last follow-up. Results were compared to a control cohort of R/R ALL patients treated with tisagenlecleucel but without preceding InO, over a contemporaneous period, at the largest paediatric CAR-T centre in the UK. Results: Fourteen patients from 5 paediatric and young adult centres in the UK received InO after screening for CAR-T therapy. InO was used pre-leucapheresis, as bridging and for both in 2, 11 and 1 respectively. Two were excluded from outcome analysis (1 adolescent with Trisomy 21 and transfusion induced hepatic siderosis died due to VOD while awaiting CAR-T production and 1 failed CAR-T manufacture despite achieving an adequate T cell harvest as per manufacturer guidance). Twelve (85%) patients were able to receive CAR-T infusion at a median of 1 month (range 0.7-5.6 months) from first InO dose. InO was well tolerated with 21% developing febrile neutropenia and grade 4 cytopenias. Use of InO pre-leucapheresis led to successful manufacture of CAR-T cells in 2/3 (66%). InO group was compared with 27 children who received CAR-T without preceding InO over the same time period. Table 1 summarises patient and CAR-T characteristics of the two groups which were comparable. Median follow-up of the I