Radiotherapy bridging in patients with R/R high-grade lymphoma receiving CD19 CAR-T in the UK
Kirkwood, A. A.
Menne, T. F.
Besley, C. M.
Beasley, M. J.
Latif, A. L.
Stevens, A. M.
Marzolini, M. A. V.
Johnson, R. J.
AffiliationKing’s College NHS Trust, London, United Kingdom
MetadataShow full item record
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.
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.
JournalInternational Journal of Radiation Oncology Biology Physics
TypeMeetings and Proceedings