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dc.contributor.authorKuhnl, A.
dc.contributor.authorMikhaeel, G.
dc.contributor.authorKirkwood, A. A.
dc.contributor.authorMenne, T. F.
dc.contributor.authorFrew, J.
dc.contributor.authorTholouli, E.
dc.contributor.authorPatel, A.
dc.contributor.authorBesley, C. M.
dc.contributor.authorBeasley, M. J.
dc.contributor.authorLatif, A. L.
dc.contributor.authorO'Rourke, N.
dc.contributor.authorNicholson, E.
dc.contributor.authorAlexander, E.
dc.contributor.authorChaganti, S.
dc.contributor.authorStevens, A. M.
dc.contributor.authorMarzolini, M. A. V.
dc.contributor.authorJohnson, R. J.
dc.contributor.authorSanderson, R.
dc.contributor.authorSivabalasingham, S.
dc.contributor.authorRoddie, C.
dc.date.accessioned2022-01-11T11:59:53Z
dc.date.available2022-01-11T11:59:53Z
dc.date.issued2021en
dc.identifier.citationKuhnl A, Mikhaeel G, Kirkwood AA, Menne TF, Frew J, Tholouli E, et al. Radiotherapy Bridging in Patients With R/R High-Grade Lymphoma Receiving CD19 CAR-T in the UK Vol. 111, International Journal of Radiation Oncology*Biology*Physics. Elsevier BV; 2021. p. S130.en
dc.identifier.doi10.1016/j.ijrobp.2021.07.296en
dc.identifier.urihttp://hdl.handle.net/10541/624903
dc.description.abstractPurpose/Objective(s) Radiotherapy (RT) has potential synergistic effects with CD19 CAR-T but is not yet widely used as bridging therapy for lymphoma. Comprehensive outcome data of RT bridged patients are limited, and selection criteria for RT bridging and optimal dose / fractionation are unknown. We hypothesized that RT is a safe, well tolerated and effective bridging to CAR-T even in patients with advanced stage and high-risk features. We analyzed details of RT bridging in a prospective national CAR-T cohort, examining patient, disease and treatment factors which may affect outcome of RT bridging. Materials/Methods We analyzed consecutive patients with r/r high-grade lymphoma who had leukapheresis for axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between Dec 2018 - Nov 2020 in 10 UK centers and received RT bridging. Results Of 371 leukapheresed patients, 76 (21%) received RT bridging (61 RT alone, 15 combined modality treatment (CMT)). Median age was 58 years. 65% had de novo diffuse large B-cell lymphoma, 7% primary mediastinal B-cell, and 28% transformed lymphoma. 64 were infused (50 axi-cel, 14 tisa-cel), with a median turnaround time of 44 days from apheresis to infusion. 12/75 (16%) patients did not proceed to CAR-T infusion (6 progressive disease (PD), 4 deaths (not related to RT), 1 manufacturing failure, 1 CR after bridging). The dropout rates were 11%, 33% & 22% for RT, CMT and chemotherapy-bridged patients respectively (P = 0.086). Disease characteristics were similar in RT & CMT groups; the majority had advanced stage (71% and 86%), 34% & 43% bulky disease, 59% & 73% extranodal involvement, 55% & 57% were primary refractory to R-CHOP, 75% & 67% had SD/PD as best response to last treatment, 18% & 13% had prior autologous transplant, and 31% & 33% had double/triple hit or -expression. In-field response in 53 cases bridged with RT alone (doses 20 – 40Gy) was 85% (11/14) for early stage (3 CR) and 63% (22/35) for advanced stage. Details of the radiation techniques and RT-related toxicities will be provided at the meeting. The ongoing overall response rate at 3 months post infusion was 63% (50% CR). With a median follow-up of 11.5 months, the median time to progression has not been reached. The 6- & 12-months event-free survival was 60% (95% CI: 47-71) and 58% (95% CI: 45 -69), respectively, with no significant difference between RT and CMT. The median overall survival (OS) was 17.8 months (95% CI: 8.9-NR), with 6- & 12-months OS rates of 77% (95% CI: 64 – 86) and 65% (95% CI: 50-76). Post CAR-T toxicity was favorable, with 7/64 (11%) experiencing G3/4 cytokine release syndrome, 8/64 (13%) G3/4 neurotoxicity. Treatment-related mortality was 4.6%. Conclusion RT is a safe and effective bridging therapy prior to CD19 CART in lymphoma. In this large prospective real world national cohort with high proportion of advanced stage and high-risk features, RT bridging was given successfully with low dropout rate and excellent survival outcomes.en
dc.titleRadiotherapy bridging in patients with R/R high-grade lymphoma receiving CD19 CAR-T in the UKen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentKing’s College NHS Trust, London, United Kingdomen
dc.identifier.journalInternational Journal of Radiation Oncology Biology Physicsen
dc.description.noteen]
refterms.dateFOA2022-04-13T09:38:00Z


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