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J.M. Logue et al.
identify if patients relapsing post-CAR T have unique infectious risks.
CAR T-cell therapy provides durable remissions in 40-50% of R/R LBCL patients. As more patients receive this therapy and have prolonged remissions, we will need to understand and manage the unique survivorship issues that occur. Here we report that patients in remission after axi-cel have prolonged immunosuppression, with CD4 T- cell counts in particular remaining low for at least 1 year, and are at risk of infection in the short and long term.
Disclosures
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 con- sultant 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.
Contributions
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.
All authors contributed to the writing of the manuscript.
Funding
This work was supported by NCI P30 CA076292 and NCI K23-CA201594.
References
1. Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabta- gene ciloleucel in refractory large B-cell lym- phoma (ZUMA-1): a single-arm, multicen- tre, phase 1-2 trial. Lancet Oncol. 2019; 20(1):31-42.
2.Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544.
3. Hill JA, Li D, Hay KA, et al. Infectious com- plications of CD19-targeted chimeric anti- gen receptor-modified T-cell immunothera- py. Blood. 2018;131(1):121-130.
4.Jain MD, Davila ML. Concise review: emerging principles from the clinical appli- cation of chimeric antigen receptor T cell therapies for B cell malignancies. Stem Cells. 2018;36(1):36-44.
5. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014; 124(2):188-195.
6.Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47-62.
7. Locke FL, Go WY, Neelapu SS. Development and use of the anti-CD19 chimeric antigen receptor T-cell therapy axi- cabtagene ciloleucel in large B-cell lym- phoma: a review. JAMA Oncol. 2019:1-10.
8. Fried S, Avigdor A, Bielorai B, et al. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019;54(10):1643-1650.
9.Shalabi H, Shah NN, Fry TJ, Yates B, Delbrook C. Chimeric antigen receptor induced cytopenia differs from chemothera- py induced myelosuppression. Blood. 2017; 130(Suppl 1):S5048.
10. Kochenderfer JN, Somerville RPT, Lu T, et al. Long-duration complete remissions of dif- fuse large B cell lymphoma after anti-CD19 chimeric antigen receptor T cell therapy. Mol Ther. 2017;25(10):2245-2253.
11.Schuster SJ, Svoboda J, Chong EA, et al. Chimeric antigen receptor T cells in refracto- ry B-cell lymphomas. N Engl J Med. 2017;377(26):2545-2554.
12.Locke FL, Neelapu SS, Bartlett NL, et al. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017;25(1):285-295.
13.Joffe E, Ariela Arad N, Bairey O, et al. Persistently low lymphocyte counts after FCR therapy for chronic lymphocytic leukemia are associated with longer overall survival. Hematol Oncol. 2018;36(1):128- 135.
14.Ysebaert L, Gross E, Kuhlein E, et al. Immune recovery after fludarabine- cyclophosphamide-rituximab treatment in B-chronic lymphocytic leukemia: implica- tion for maintenance immunotherapy. Leukemia. 2010;24(7):1310-1316.
15. Park JH, Romero FA, Taur Y, et al. Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lym- phoblastic leukemia treated with chimeric antigen receptor T cells. Clin Infect Dis. 2018;67(4):533-540.
16. Annibali O, Hohaus S, Marchesi F, et al. The neutrophil/lymphocyte ratio >/=3.5 is a prognostic marker in diffuse large B-cell lymphoma: a retrospective analysis from the database of the Italian regional network 'Rete Ematologica del Lazio per i Linfomi' (RELLI). Leuk Lymphoma. 2019; 60(14): 3386-3394.
17. Porrata LF, Ristow K, Habermann T, et al. Predicting survival for diffuse large B-cell lymphoma patients using baseline neu- trophil/lymphocyte ratio. Am J Hematol. 2010;85(11):896-899.
18. Hill JA, Krantz EM, Hay KA, et al. Durable preservation of antiviral antibodies after CD19-directed chimeric antigen receptor T- cell immunotherapy. Blood Adv. 2019;3( 22):3590-3601.
19. Hashmi H, Bachmeier C, Chavez JC, et al. Haemophagocytic lymphohistiocytosis has variable time to onset following CD19 chimeric antigen receptor T cell therapy. Br J Haematol. 2019;187(2):e35-e38.
20. Nonomura Y, Yasumoto M, Yoshimura R, et al. Relationship between bone marrow cel- lularity and apparent diffusion coefficient. J Magn Reson Imaging. 2001;13(5):757-760.
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