PMID- 37171599 OWN - NLM STAT- MEDLINE DCOM- 20230614 LR - 20230614 IS - 1432-0584 (Electronic) IS - 0939-5555 (Linking) VI - 102 IP - 7 DP - 2023 Jul TI - Efficacy and safety-related factors of BTK inhibitors as a bridge to CAR-T therapy in R/R FL. PG - 1789-1799 LID - 10.1007/s00277-023-05255-w [doi] AB - Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy has achieved satisfactory results in relapsed/refractory (R/R) follicular lymphoma (FL), patients with R/R FL and high-risk disease characteristics, previous hematopoietic stem cell transplantation, bulky disease, and progression of disease within 2 years (POD24) had a low complete response (CR). Twenty-seven patients with R/R FL, later disease stages, higher tumor burden, or higher previous treatment lines who had received Bruton tyrosine kinase (BTK) inhibitors before anti-CD19 CAR T cell therapy, or received BTK inhibitors as combination therapy, were included in this study. The clinical response and adverse events (AEs) in anti-CD19 CAR T cell therapy were observed. All patients with R/R FL who received BTK inhibitors combined with anti-CD19-CAR T cell therapy had later disease stages, higher tumor burden, and higher treatment lines than those who did not receive BTK inhibitor combination therapy. However, no difference in the clinical response was found between the two groups. The clinical response in the POD24 group was lower than that in the non-POD24 group; however, no difference in the clinical response was found between the FL and transformed FL (tFL) groups, between the follicular lymphoma international prognostic index (FLIPI) 1 1-2 and FLIPI 1 3-5 groups, and between the FLIPI 2 1-2 and FLIPI 2 3-5 groups. The mean anti-CD19 CAR T cell peak was higher in the CAR-T group with BTK inhibitor than in the CAR-T group without BTK inhibitor. Meanwhile, a higher proportion of patients in the non-POD24 group, FL group, and PR group achieved CR after 2 months. No difference in cytokine secretion was found between the CAR-T group with and without BTK inhibitors. It was higher in the non-POD24 group, FLIPI 1 3-5 group, and FLIPI 2 3-5 group. No difference in cytokine release syndrome and immune effector cell-associated neurotoxic syndrome grades was found between the CAR-T groups with or without BTK inhibitors and between the other groups. Poor prognostic factors, other than POD24, did not affect the clinical response to BTK inhibitors in combination with anti-CD19 CAR T cell therapy in patients with R/R FL. Therefore, BTK inhibitors combined with anti-CD19 CAR-T therapy may be an effective and safe approach for patients with R/R FL and high-risk factors.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. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Ye, Xiupeng AU - Ye X AD - Department of Hematology, People's Hospital of Ningxia Hui Autonomous Region, 301 Zhengyuan North Street, Jinfeng District, Yinchuan City, 750002, Ningxia, China. FAU - Fan, Xuemei AU - Fan X AD - The First Central Clinical College of Tianjin Medical University, Tianjin, 300070, China. FAU - Cui, Rui AU - Cui R AD - Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, 24 Fukang Road, Tianjin, 300192, China. FAU - Mu, Juan AU - Mu J AD - Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, 24 Fukang Road, Tianjin, 300192, China. FAU - Liu, Meijing AU - Liu M AD - Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, 24 Fukang Road, Tianjin, 300192, China. FAU - Lyu, Cuicui AU - Lyu C AD - Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, 24 Fukang Road, Tianjin, 300192, China. FAU - Li, Yeqiong AU - Li Y AD - Department of Hematology, People's Hospital of Ningxia Hui Autonomous Region, 301 Zhengyuan North Street, Jinfeng District, Yinchuan City, 750002, Ningxia, China. FAU - Chen, Lan AU - Chen L AD - Department of Hematology, People's Hospital of Ningxia Hui Autonomous Region, 301 Zhengyuan North Street, Jinfeng District, Yinchuan City, 750002, Ningxia, China. FAU - Zhang, Jin AU - Zhang J AD - Department of Hematology, People's Hospital of Ningxia Hui Autonomous Region, 301 Zhengyuan North Street, Jinfeng District, Yinchuan City, 750002, Ningxia, China. FAU - Li, Xin AU - Li X AD - Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, 24 Fukang Road, Tianjin, 300192, China. FAU - Wang, Jia AU - Wang J AD - Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, 24 Fukang Road, Tianjin, 300192, China. FAU - Mou, Nan AU - Mou N AD - Shanghai Genbase Biotechnology Co., Ltd., 326 Edison Road, Shanghai, 201203, China. FAU - Deng, Qi AU - Deng Q AUID- ORCID: 0000-0002-3646-4953 AD - Department of Hematology, Tianjin First Central Hospital, School of Medicine, Nankai University, 24 Fukang Road, Tianjin, 300192, China. yxp4200338@163.com. LA - eng GR - 2021BEG03036/Education Department of Ningxia Hui Autonomous Region/ PT - Journal Article DEP - 20230512 PL - Germany TA - Ann Hematol JT - Annals of hematology JID - 9107334 RN - 0 (Receptors, Chimeric Antigen) RN - 0 (Antigens, CD19) SB - IM MH - Humans MH - Immunotherapy, Adoptive/adverse effects MH - *Lymphoma, Follicular/etiology MH - *Receptors, Chimeric Antigen MH - Neoplasm Recurrence, Local MH - *Lymphoma, Non-Hodgkin/etiology MH - Antigens, CD19 OTO - NOTNLM OT - Bruton tyrosine kinase inhibitors OT - Chimeric antigen receptor (CAR) OT - Efficacy OT - Follicular lymphoma OT - Side effects EDAT- 2023/05/12 13:08 MHDA- 2023/06/14 06:42 CRDT- 2023/05/12 11:13 PHST- 2023/01/31 00:00 [received] PHST- 2023/04/29 00:00 [accepted] PHST- 2023/06/14 06:42 [medline] PHST- 2023/05/12 13:08 [pubmed] PHST- 2023/05/12 11:13 [entrez] AID - 10.1007/s00277-023-05255-w [pii] AID - 10.1007/s00277-023-05255-w [doi] PST - ppublish SO - Ann Hematol. 2023 Jul;102(7):1789-1799. doi: 10.1007/s00277-023-05255-w. Epub 2023 May 12.