Improved outcomes of large B-cell lymphoma patients treated with CD19 CAR T in the UK over time.
T cells
cancer
cellular therapies
non-Hodgkins lymphoma
outcomes
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
17 Oct 2023
17 Oct 2023
Historique:
revised:
11
09
2023
received:
08
07
2023
accepted:
03
10
2023
medline:
18
10
2023
pubmed:
18
10
2023
entrez:
17
10
2023
Statut:
aheadofprint
Résumé
The success of CD19 Chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off-the-shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the 'standard-of-care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020-2022). We identified significant improvements for Era 2 versus Era 1 in dropout rate (17% vs. 27%, p = 0.001), progression-free survival (1-year PFS 50% vs. 32%, p < 0.001) and overall survival (1-year OS 60% vs. 40%, p < 0.001). We also observed increased use of bridging therapy, improvement in bridging outcomes, more tocilizumab/corticosteroid use, reduced high-grade cytokine release syndrome (4% vs. 9%, p = 0.01) and intensive care unit admissions (20% vs. 32%, p = 0.001). Our results demonstrate significant improvement in CAR T outcomes over time, highlighting the importance of using up-to-date clinical data when comparing CAR T against new treatment options for r/r LBCL.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 British Society for Haematology and John Wiley & Sons Ltd.
Références
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544.
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory DLBCL. N Engl J Med. 2019;380:45-56.
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396:839-852.
Nastoupil LJ, Jain MD, Feng L, Spiegel JY, Ghobadi A, Lin Y, et al. Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US lymphoma CAR T consortium. J Clin Oncol. 2020;38:3119-3128.
Kwon M, Iacoboni G, Reguera JL, Corral LL, Morales RH, Ortiz-Maldonado V, et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. Haematologica. 2023;108:110-121.
Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, et al. GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany. Blood. 2022;140:349-358. https://doi.org/10.1182/blood.2021015209
Kuhnl A, Roddie C, Kirkwood AA, Tholouli E, Menne T, Patel A, et al. A national service for delivering CD19 CAR-T in large B-cell lymphoma - the UK real-world experience. Br J Haematol. 2022;198:492-502. https://doi.org/10.1111/bjh.18209
Bachy E, le Gouill S, di Blasi R, Sesques P, Manson G, Cartron G, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022;28:2145-2154.
Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387:2220-2231.
Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2022;41:2238-2247. https://doi.org/10.1200/jco.22.01725
Jacobson CA, Hunter BD, Redd R, Rodig SJ, Chen PH, Wright K, et al. Axicabtagene ciloleucel in the non-trial setting: outcomes and correlates of response, resistance, and toxicity. J Clin Oncol. 2020;38:3095-3106.
Sanderson R, Kuhnl A, Tholouli E, Menne TF, Patel A, Chaganti S, et al. CAR-T toxicity management and steroid use in high-grade B-cell lymphoma: impact on real-world survival outcomes in the UK. Blood. 2021;138:531.
Topp M, van Meerten T, Houot R, Minnema MC, Milpied N, Lugtenburg PJ, et al. Earlier steroid use with axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory large B cell lymphoma. Blood. 2019;134:243.
Oluwole OO, Bouabdallah K, Muñoz J, de Guibert S, Vose JM, Bartlett NL, et al. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021;194:690-700.
Vercellino L, di Blasi R, Kanoun S, Tessoulin B, Rossi C, D'Aveni-Piney M, et al. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020;4:5607-5615.
Roddie C, Neill L, Osborne W, Iyengar S, Tholouli E, Irvine D, et al. Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma. Blood Adv. 2023;7:2872-2883. https://doi.org/10.1182/bloodadvances.2022009019
Boyle S, Kuhnl A, Correia de Farias M, Patten PE, Yallop D, Benjamin R, et al. P1169: elevated CRP AT infusion of axicabtagene ciloleucel predicts high-grade CAR-T toxicity and outperforms more complex scores. Hemasphere. 2022;6:1055-1056.
Jacobson CA, Locke FL, Ma L, Asubonteng J, Hu ZH, Siddiqi T, et al. Real-world evidence of axicabtagene ciloleucel for the treatment of large B cell lymphoma in the United States. Transplant Cell Ther. 2022;28:581.e1-581.e8.
Landsburg DJ, Frigault M, Heim M, Foley SR, Hill BT, Ho CM, et al. Real-world outcomes for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin's lymphoma (aBNHL) treated with commercial tisagenlecleucel: subgroup analyses from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. Blood. 2022;140:1584-1587.
Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L, et al. CAR-HEMATOTOX: a model for CAR T-cell related hematological toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499-2513. https://doi.org/10.1182/blood.2020010543