PMID- 32327504 OWN - NLM STAT- MEDLINE DCOM- 20210527 LR - 20230223 IS - 1592-8721 (Electronic) IS - 0390-6078 (Print) IS - 0390-6078 (Linking) VI - 106 IP - 4 DP - 2021 Apr 1 TI - Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. PG - 978-986 LID - 10.3324/haematol.2019.238634 [doi] AB - CD19 CAR T-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with >= grade 3 neutropenia seen in 21/70 (30-0%) patients at day 30 and persisting in 3/31 (9-7%) patients at 1 year. B cells were undetectable in 30/34 (88-2%) patients at day 30, but were detected in 11/19 (57-9%) at 1 year. Median IgG levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/mul at 1 year after axi-cel (n=19, range 33 - 269). In total, 23/85 (27-1%) patients received IVIG after axi-cel, and 34/85 (40-0%) received G-CSF. Infections in the first 30 days occurred in 31/85 (36-5%) patients, of which 11/85 (12-9%) required intravenous antibiotics or hospitalization ("severe") and were associated with cytokine release syndrome (CRS), neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, 7 severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T cell immunosuppression without severe infection. FAU - Logue, Jennifer M AU - Logue JM AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Zucchetti, Elisa AU - Zucchetti E AD - Ospedale Niguarda Ca' Granda, Milan, Italy. FAU - Bachmeier, Christina A AU - Bachmeier CA AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Krivenko, Gabriel S AU - Krivenko GS AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Larson, Victoria AU - Larson V AD - Morsani College of Medicine, University of South Florida, Tampa, FL, USA. FAU - Ninh, Daniel AU - Ninh D AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Grillo, Giovanni AU - Grillo G AD - Ospedale Niguarda Ca' Granda, Milan, Italy. FAU - Cao, Biwei AU - Cao B AD - Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. FAU - Kim, Jongphil AU - Kim J AD - Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. FAU - Chavez, Julio C AU - Chavez JC AD - Dept. of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. FAU - Baluch, Aliyah AU - Baluch A AD - Dept. of Infectious Diseases, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. FAU - Khimani, Farhad AU - Khimani F AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Lazaryan, Aleksandr AU - Lazaryan A AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Nishihori, Taiga AU - Nishihori T AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Liu, Hien D AU - Liu HD AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Pinilla-Ibarz, Javier AU - Pinilla-Ibarz J AD - Dept of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. FAU - Shah, Bijal D AU - Shah BD AD - Dept of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. FAU - Faramand, Rawan AU - Faramand R AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Coghill, Anna E AU - Coghill AE AD - Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. FAU - Davila, Marco L AU - Davila ML AD - Dept. of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. FAU - Dholaria, Bhagirathbhai R AU - Dholaria BR AD - Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Jain, Michael D AU - Jain MD AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. FAU - Locke, Frederick L AU - Locke FL AD - Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA. LA - eng GR - K12 CA090625/CA/NCI NIH HHS/United States GR - K23 CA201594/CA/NCI NIH HHS/United States GR - P30 CA076292/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210401 PL - Italy TA - Haematologica JT - Haematologica JID - 0417435 RN - 0 (Antigens, CD19) RN - 0 (Biological Products) RN - U2I8T43Y7R (axicabtagene ciloleucel) SB - IM MH - Antigens, CD19/therapeutic use MH - Biological Products MH - Humans MH - *Immune Reconstitution MH - *Immunotherapy, Adoptive MH - Retrospective Studies PMC - PMC8017820 EDAT- 2020/04/25 06:00 MHDA- 2021/05/28 06:00 PMCR- 2020/04/23 CRDT- 2020/04/25 06:00 PHST- 2020/08/03 00:00 [received] PHST- 2020/04/25 06:00 [pubmed] PHST- 2021/05/28 06:00 [medline] PHST- 2020/04/25 06:00 [entrez] PHST- 2020/04/23 00:00 [pmc-release] AID - haematol.2019.238634 [pii] AID - 10.3324/haematol.2019.238634 [doi] PST - epublish SO - Haematologica. 2021 Apr 1;106(4):978-986. doi: 10.3324/haematol.2019.238634.