• Real-world data of high-grade lymphoma patients treated with CD19 CAR-T in the UK

      Kuhnl, A.; Roddie, C.; Tholouli, E.; Menne, T.; Linton, K.; Lugthart, S.; Chaganti, S.; Sanderson, R.; O'Reilly, M.; Norman, J.; et al. (2020)
      Background: England was the ?rst European country to commission a national service for the delivery of CD19 CAR-T in high-grade lymphoma. Since December 2018, relapsed/refractory (r/r) high-grade lymphoma patients who failed two or more lines of treatment have had access to CD19 CAR-T through the NHSE Cancer Drug Fund (CDF). Treatment is delivered at seven commissioned centres in England (QEHB Birmingham, University Hospital Bristol, KCH London, UCLH, The Christie Manchester, Manchester MRI, Freeman Hospital Newcastle). In addition, CAR-T centres in Glasgow and Cardiff have recently opened, alongside a second wave of centres in England (Cambridge, Leeds, RMH London), allowing more patients access to this specialised treatment in their local area. Treatment is approved through a weekly National CAR-T Clinical Panel (NCCP). Here, we report results of the ?rst 125 lymphoma patients approved by the panel between December 2018 and July 2019.Methods: All patients with r/r high-grade lymphoma referred to the NCCP between December 2018 and July 2019 and deemed eligible for treatment with CD19 CAR-T were analysed. Eligibility was assessed according to CDF criteria and con?rmed at the centre's CAR-T multidisciplinary team meeting. The ?nal decision on patient eligibility was made by consensus through the NCCP independent panel. The choice of CAR-T product (axicabtagene ciloleucel (axicel) or tisagenlecleucel (tisagen)) was at the discretion of the treating centre. Results: A total of 133 cases were submitted to the NCCP of which 125 were approved for treatment with CD19 CAR-T. Seventy-nine patients were selected for axi-cel and 46 for tisagen. In total, 116 patients underwent leukapheresis and 91 proceeded to infusion. In the intention to treat (ITT) population, patients? median age was 62 years (range 18?75), 26% were 65 years or older. 89 (71%) patients had de novo diffuse large B-cell lymphoma, 23 (18%) transformed follicular lymphoma, six (5%) transformed marginal zone lymphoma and seven (6%) primary mediastinal B-cell lymphoma. About 76% of cases were advanced stage, 33% had bulky disease and 58% extranodal involvement. About 53/125 (42%) of patients had received three or more prior lines of treatment, 20 patients had previous autologous transplant, ?ve previous allograft. 72% of patients had stable or progressive disease as best response to the last line of treatment. About 83% patients received bridging therapy between the time of NCCP approval and CAR-T infusion (57% chemotherapy, 16% steroids, 10% radiotherapy). Of the 91 patients infused, 11% experienced grade 3+ cytokine release syndrome, 13% grade 3+ neurotoxicity and 34% of patients required intensive care support. Among 80 evaluable patients, the overall response rate at 3 months was 35% (20% complete responses). About 62?5% of patients showed early progression by 3 months. Two patients died from treatment-related toxicities. With a median follow-up of 4?8 months, the median event-free survival was 3?1 months, the median overall survival (OS) has not been reached. Median OS of the ITT cohort was 9?1 months. Updated ef?cacy analyses will be presented at the meeting. Conclusion: NHSE has successfully implemented a national structure for providing broad and rapid access to licensed CD19 CAR-T products. This unique set-up allows capture of prospective real-world data of CAR-T treated patients in the UK, which will help the understanding of the clinical benefirt and health economic implications of this complex treatment in daily practice.