Real-World Data of High-Grade Lymphoma Patients Treated with CD19 CAR-T in England
Authors: Kuhnl Andrea , Roddie Claire , Martinez-Cibrian Nuria , Menne Tobias F , Linton Kim , Lugthart Sanne , Chaganti Sridhar , Sanderson Robin , Marzolini Maria A V , Norman Jane , Osborne Wendy , Radford John , Robinson Stephen , Malladi Ram , Patten Piers E.M. , O'Reilly Maeve A , Saif Muhammad , Shenton Geoff , Bloor Adrian , Rowntree Clare J , Irvine David A. , Stewart Orla , Ardavan Arzhang , Robinson Kate , Pagliuca Antonio , Bowles Kristian M , Collins Graham P. , Johnson Rod , McMillan Andrew K 
Published: February 2020

Background
After European Medicines Agency (EMA) approval of axicabtagene ciloleucel and tisagenlecleucel for the treatment of relapsed/refractory (r/r) high-grade lymphoma in 2018, England was one of the first European countries granting fully funded access to these CD19 CAR-T therapies. Both products are available through the National Health Service England (NHSE) Cancer Drug Fund until their cost-effectiveness has been determined. The NHSE CAR-T program has been set up in a structure aiming to implement robust and transparent criteria for patient selection and to ensure equity of treatment access: CAR-T slots are approved by a weekly National CAR-T Clinical Panel (NCCP), consisting of independent clinical experts, patient representatives, and delegates from each CAR-T centre; treatment is delivered in 7 geographically spread commissioned CAR-T centres (Birmingham, Bristol, King's College Hospital London, University Hospital London, The Christie Manchester, Manchester Royal Infirmary, Newcastle). Here, we report prospective data on the first 122 lymphoma patients approved by the NCCP.
Methods
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 in the CAR-T centre's tumor board, based on organ function and fitness (performance status 0/1), absence of active CNS disease, and biopsy confirmation of r/r high-grade lymphoma. The final decision on patient eligibility was made by consensus through the NCCP independent clinical panel. CAR-T product selection for each patient was done by the CAR-T centre, mainly on the basis of manufacturing slot availability.
Results
122 patients were approved for treatment with CD19 CAR-T therapy by the panel. CAR-T centres selected 76 patients for axicabtagene ciloleucel and 46 for tisagenlecleucel. Patients' median age was 56 years (range 18-75). 62% were male. 87 (71%) patients had de novo diffuse large B-cell lymphoma, 29 (24%) transformed lymphoma (23 from follicular- and 6 from marginal zone lymphoma), and 6 (5%) primary mediastinal B-cell lymphoma. 96 (79%) patients had biopsy confirmation of disease prior to submission. 71 (58%) patients had received 2 prior lines of therapy for high-grade lymphoma, 51 (42%) patients 3 or more treatment lines (maximum 6). 5 patients had previous allogeneic, 19 previous autologous transplant. 88% of patients (107/122) were refractory to the last line of treatment (stable- or progressive disease (PD) or relapse within 6 months).
Among 122 patients, 112 completed leukapheresis, 3 are awaiting the procedure, and 7 patients did not proceed (6 due to PD, 1 opted for radical radiotherapy). 57 of 112 patients were infused at the time of abstract submission, 42 are awaiting CAR-T infusion. 10 patients did not proceed to infusion due to disease progression and clinical deterioration (3 with CNS relapse), 2 due to manufacturing failure. One patient achieved a complete response following bridging therapy and is currently monitored.
84% (88/105) patients received bridging therapy between the time of NCCP approval and CAR-T infusion (median 64 days), 62 had chemotherapy, 9 radiotherapy, and 17 steroids only. Details on bridging therapy, treatment-related toxicities and outcomes will be provided at the meeting, by which time approximately 62 patients will have completed their 3 months PET response assessment.
Conclusion
NHSE has successfully implemented a national structure for providing licenced CAR-T products in England, enabling equity of access and oversight on capacity and patient outcomes, which can serve as a model for newly licenced, cost-intense and complex cell- and gene therapies in the future. The prospective and centralised nature of this dataset offers a true reflection of the real-world patient population undergoing CAR-T therapy in England.

Disclosures
Kuhnl: Kite Gilead: Honoraria. Roddie:Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy. Menne:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Kyowa Kirin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau. Sanderson:Kite/Gilead: Honoraria. Osborne:Novartis: Other: Travel; Pfizer: Honoraria, Speakers Bureau; MSD: Consultancy; Takeda: Consultancy, Honoraria, Other: Travel, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Speakers Bureau; Servier: Consultancy; Gilead: Consultancy. Radford:AstraZeneca: Equity Ownership, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Research Funding; GSK: Equity Ownership; Seattle Genetics: Consultancy, Honoraria. Patten:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Roche: Honoraria, Research Funding. O'Reilly:Kite Gilead: Honoraria. Bloor:Abvie, Gilead, Novartis, Autolus, Celgene, etc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational grant. Rowntree:Novartis: Consultancy. Bowles:Abbvie: Research Funding; Janssen: Research Funding. Collins:Gilead: Consultancy, Honoraria. McMillan:BMS: Honoraria; Celgene: Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Gilead: Honoraria; Novartis: Honoraria; Sandoz: Honoraria; Pfizer: Honoraria, Research Funding; MSD: Honoraria.