Efficacy and safety related factors of BTK inhibitors as a bridge to CAR-T therapy in R/R FL

Background: Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy has achieved satisfactory results in relapsed/refractory (R/R) Follicular lymphoma (FL), R/R FL patients with high-risk disease characteristics, previous HSCT, bulky disease, and POD24 had a low complete response (CR). Patients and methods: Twenty-seven R/R FL patients with higher advanced disease stage, higher tumor burden or higher previous treatment lines had already received Bruton tyrosine kinase (BTK) inhibitors prior to anti-CD19-CAR T-cell therapy, or received BTK inhibitors as combination/maintenance therapy in this study. The clinical response and adverse events (AEs) were observed in this study. Results: : All R/R FL patients who received BTK inhibitors prior to the study had higher advanced disease stage, tumor burden, and previous treatment lines than those who did not receive BTK inhibitors. Patients who received combination/maintenance therapy with BTK inhibitors had higher advanced disease stage and tumor burden than those who did not receive BTK inhibitors. There was no difference of POD 24, TP53, tFL, IPI score in the three groups with or without BTK inhibitors. The clinical response was lower in POD 24 group than that of in no POD 24 group. But the other poor prognostic factors did not affect the clinical response with the methods of BTK inhibitors as a bridge to CAR-T cell therapy or a combination/maintenance treatment with CAR-T cell therapy. There was no difference of the mean peaks of anti-CD19-CAR T cells in three groups with or without BTK inhibitors. It was higher in no POD 24 group and in FL group. But it was no difference between the FLIPI 1 1-2 and FLIPI 1 3-5 group, the FLIPI 2 1-2 and FLIPI 2 3-5 group. The CRS grades were higher in BTK inhibitors before CAR-T cell therapy group, no POD 24 group, FL group, FLIPI 3-5 grade group. The ICANS grade was higher in BTK inhibitors before CAR-T cell therapy group. Conclusion: Other poor prognostic factors except POD 24 did not affect clinical response with the methods of BTK inhibitors as a bridge to anti-CD19-CAR T cell therapy or a combination/maintenance treatment with CAR-T cell therapy in R/R FL patients. Trial registration: The study was registered at http://www.chictr.org.cn/index.aspx as ChiCTR-ONN-16009862 and http://www.chictr.org.cn/index.aspx as ChiCTR1800019622.