Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma

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 recon...

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Veröffentlicht in:Haematologica (Roma) Jg. 106; H. 4; S. 978 - 986
Hauptverfasser: Logue, Jennifer M, Zucchetti, Elisa, Bachmeier, Christina A, Krivenko, Gabriel S, Larson, Victoria, Ninh, Daniel, Grillo, Giovanni, Cao, Biwei, Kim, Jongphil, Chavez, Julio C, Baluch, Aliyah, Khimani, Farhad, Lazaryan, Aleksandr, Nishihori, Taiga, Liu, Hien D, Pinilla-Ibarz, Javier, Shah, Bijal D, Faramand, Rawan, Coghill, Anna E, Davila, Marco L, Dholaria, Bhagirathbhai R, Jain, Michael D, Locke, Frederick L
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Italy Fondazione Ferrata Storti 01.04.2021
Ferrata Storti Foundation
Schlagworte:
Antigens, CD19 - therapeutic use
Biological Products
Humans
Immune Reconstitution
Immunotherapy, Adoptive
Retrospective Studies
ISSN:0390-6078, 1592-8721, 1592-8721
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Zusammenfassung: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/μl 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.
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MDJ and FLL designed and supervised the research; KML, EZ, CAB, GSK, VL and DN collected and analyzed data; GG, BC and JK provided statistical analysis; JCC, AB, FK, AL, TN, HDL, JP, BDS, RF, AEC, MLD and BRD provided patient information and data.
Disclosures
Contributions
CB sits on the Advisory Board for Kite/Gilead; JCCh sit on the Advisory Board for Kite/Gilead, Novartis, Bayer, Genetech and is a member of the Speaker Bureau for Genetech; BDS has is a consultant for Celgene/Juno, Adaptive, Kite/Gilead, Novartis, Pharmacyclics, Spectrum/Acroteca and AstraZeneca and has received research funding from Jazz and Incyte; JP-I is a consultant for Takeda, Abbvie, Janssen, Novartis, Gilead and Teva; MLD has received research funding from Celgene, Novartis, Atara and other financial support from Novartis, Precision Biosciences, Celyad, Bellicum, GlaxoSmithKline and holds stock options from Precision Biosciences, Adaptive Biotechnologies, Anixa Biosciences; FLL is a Consultant for Cellular Biomedicine Group, Inc. and a scientific advisor for Kite/Gilead, Novartis, and MDJ is consultant for Kite/Gilead and Novartis.
All authors contributed to the writing of the manuscript.
ISSN:0390-6078
1592-8721
1592-8721
DOI:10.3324/haematol.2019.238634