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Ferrata Storti Foundation
Haematologica 2021 Volume 106(4):978-986
Cell Therapy & Immunotherapy
Immune reconstitution and associated infections following axicabtagene ciloleucel
in relapsed or refractory large B-cell lymphoma
Jennifer M. Logue,1,2* Elisa Zucchetti,3* Christina A. Bachmeier,1
Gabriel S. Krivenko,1 Victoria Larson,2 Daniel Ninh,1 Giovanni Grillo,3
Biwei Cao,4 Jongphil Kim,4 Julio C. Chavez,2,5 Aliyah Baluch,2,6
Farhad Khimani,1,2 Aleksandr Lazaryan,1,2 Taiga Nishihori,1,2 Hien D. Liu,1,2 Javier Pinilla-Ibarz,2,5 Bijal D. Shah,2,5 Rawan Faramand,1,2 Anna E. Coghill,7 Marco L. Davila,1,2 Bhagirathbhai R. Dholaria,1,8 Michael D. Jain1,2# and Frederick L. Locke1,2#
1Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Morsani College of Medicine, University of South Florida, Tampa, FL, USA; 3Divisione di Ematologia, Centro Trapianti di Midollo, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 4Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 5Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 6Department of Infectious Diseases, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 7Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA and 8Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
*JML and EZ contributed equally as co-first authors. #MDJ and FLL contributed equally as co-senior authors
ABSTRACT
CD19 chimeric antigen receptor T (CAR T)-cell therapy with axicab- tagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B-cell lymphoma (LBCL) may lead to durable remissions, however, pro- longed cytopenias and infections may occur. In this single center retrospec- tive 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 of 70 (30%) patients at day 30 and persisting in 3 of 31 (9.7%) patients at 1 year. B cells were unde- tectable in 30 of 34 (88.2%) patients at day 30, but were detected in 11 of 19 (57.9%) at 1 year. Median immunoglobulin G levels 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/mL at 1 year after axi-cel (n=19, range: 33– 269). In total, 23 of 85 (27.1%) patients received intravenous immunoglobulins after axi-cel, and 34 of 85 (40%) received granulocyte-colony stimulating factor. Infections in the first 30 days occurred in 31 of 85 (36.5%) patients, of which 11 of 85 (12.9%) required intravenous antibiotics or hospitalization (“severe”) and were associated with cytokine release syndrome, neurotoxicity, tocilizumab use, corticos- teroid use, and bridging therapy on univariate analyses. After day 30, seven 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.
Introduction
Axicabtagene ciloleucel (axi-cel) can lead to long term disease control for patients with R/R LBCL, including diffuse (DLBCL), primary mediastinal (PMBCL), and transformed follicular lymphoma (tFL). In the pivotal ZUMA-1 trial, axi-cel led to a best objective response rate (ORR) of 82% and complete response (CR) rate of 54%, with 2-year follow-up data reporting durable responses and median overall
Correspondence:
FREDERICK L. LOCKE
frederick.locke@moffitt.org
MICHAEL D. JAIN
michael.jain@moffitt.org
Received: September 21, 2019. Accepted: April 2, 2020. Pre-published: April 23, 2020.
https://doi.org/10.3324/haematol.2019.238634
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