• National implementation of the use of tisagenlecleucel in paediatric and young adult patients with acute lymphoblastic leukaemia (ALL) in National Health Service England (NHSE)

      Furness, C. L.; Hough, R.; Cummins, M.; Murphy, G.; Ghorashian, S.; Amrolia, P.; Roddie, C.; O'Reilly, M.; Wynn, R.; Bonney, D.; et al. (2020)
      Background: Following European Medicines Agency (EMA) approval of Tisagenlecleucel (KYMRIAH®) for the treatment of relapsed/refractory acute lymphoblastic leukaemia (ALL) in children and young adults in 2018, England established a structured funding programme via the National Health Service England (NHSE) Cancer Drugs Fund. Methods: NHSE established a national CAR-T clinical panel for ALL (NCCP ALL). The aim of the NCCP ALL was to review cases to confirm eligibility against published criteria in line with the ELIANA study inclusion criteria and ensure prompt national access to Tisagenlecleucel. All CAR-T centres (3 open at NCCP set up and 9 open at 1 year review) were accredited for the Immune Effector Cell Standards in the 7th edition of the JACIE Standards in line with EBMT/JACIE recommendations (Yakoub-Agha et al 2019). The NCCP ALL consisted of representatives from NHSE, CAR-T centres, patient representation and independent ALL clinical experts. We describe panel experience over a one year period. Results: The NCCP met by weekly teleconference to review cases referred by individual CAR-T centre lead clinicians who endorsed eligibility. Approval for access to Tisagenlecleucel was granted through unanimous panel consensus agreement following review of eligibility criteria (according to disease and CD19+ status, absence of CNS disease, performance status and organ function). Allocation to centre was achieved by review of geography, slot availability and patient preference. From 19.11.2018-18.11.2019 34 patients were approved (age range 9 months - 21 years, median age 10.5 years). 5 did not proceed to leukapheresis (2 incorrect diagnosis of relapse, 1 received alternative CAR-T clinical trial product, 2 unable to proceed due to disease progression/complications). At time of abstract submission 23/29 (79.3%) patients had undergone CAR-T infusion. 3 patients who underwent leukapheresis were unable to proceed to infusion (1 patient due to emergence of CD19 negative disease, 1 patient due to CNS disease progression, 1 patient received cranial radiotherapy to control CNS disease and suffered frank bone marrow relapse treated with Inotuzumab followed by a failed manufacture). 3 patients await infusion. Mean time from panel approval to leukapheresis was 15 days (range 0-47 days) and mean time from leukapheresis to CAR-T infusion for patients infused was 64 days (range 35 - 92 days) Of 15 patients evaluable beyond 100 days (8 patients yet to reach this time point), 11 have a documented status of ‘alive in MRD negative remission’. This represents 73% patients infused (11/15). Brief toxicity and follow up data will be reported at EBMT 2020 with future planned efficacy analysis. Conclusions: The establishment of a national panel in England for Tisagenlecleucel approval has allowed prompt, equitable and trackable access to this CAR-T product for ALL. From a worldwide perspective, NHSE is one of the first health services to introduce a national co-ordinated access programme of care and will utilise programme data to assess real world outcomes for patients treated with Tisagenlecleucel.