Outcome of high-grade lymphoma patients treated with cd19 car-t-updated real-world experience in the UK

Background: After EMA approval of CD19 CAR-T for relapsed/refractory (r/r) high-grade lymphoma in 2018, several European countries have started delivering this treatment in standard practice. However, selection criteria and referral pathways are not well defined and significantly vary between countries and centres, resulting in inequity of treatment access and difficulties to adequately use and monitor health economic resources. England was the first European country to implement a national service for CD19 CAR-T using objective and transparent eligibility criteria, and other countries have started following a similar structure. Cases are reviewed and approved by a National CAR-T Clinical Panel (NCCP) and outcome data are prospectively collected. Since December 2018, treatment has been delivered at 7 commissioned CAR-T centres in England, more recently expanded to further centres in England, Scotland and Wales. We have previously presented results from the first 6 months of the CAR-T national program (Kuhnl, ASH annual meeting 2019). Aims: To provide an updated analysis of 250 lymphoma patients enrolled over 12 months. Methods: Consecutive patients with r/r high-grade lymphoma submitted to the NCCP between December 2018 and December 2019 were analysed. Eligibility was assessed at the centre's CAR-T multidisciplinary team meeting and confirmed by the NCCP independent panel. The choice of CAR-T product (axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisagen)) was at the discretion of the treating centre. Results: 272 cases have been submitted to the NCCP for treatment with CD19 CAR-T and 250 have been approved. 174 patients were selected for axi-cel and 76 for tisagen. 232 patients completed leukapheresis, 18 procedures were cancelled. 163 of 232 patients received CAR-T cells, 27 patients are awaiting infusion at the time of abstract submission. In the intention to treat population, patients' median age was 58 years (range 18-75). 174 (70%) patients had De novo diffuse large B-cell lymphoma, 13 (5%) primary mediastinal B-cell lymphoma, and 63 (25%) transformed lymphoma (49 follicular lymphoma background, 14 non-follicular indolent histology). 79% of cases were advanced stage, 31% had bulky disease and 66% extranodal involvement. 97/250 (39%) of patients had received 3 or more prior lines of treatment, 33 patients had previous autologous transplant, 5 previous allograft. 77% of patients had stable or progressive disease as best response to the last line of treatment. Details on bridging therapy, toxicities and outcomes will be provided at the meeting, with an expected number of 170 patients evaluable for the 3 months response assessment. Summary/Conclusion: The UK national CAR-T service provides an excellent structure for broad, efficient and fair access to licenced CD19 CAR-T products and can serve as a model for implementing cost-intense complex therapies on a national basis. This prospective, unselected real- world population of CAR-T eligible and -treated patients offers valuable insights into the clinical benefit and health economic implications of CD19 CAR-T in daily practice.