Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 14;7(21):6589-6598.
doi: 10.1182/bloodadvances.2023010624.

Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry

Jean Lemoine  1 , Emmanuel Bachy  2 , Guillaume Cartron  3 , David Beauvais  4 , Thomas Gastinne  5 , Roberta Di Blasi  6 , Marie-Thérèse Rubio  7 , Stéphanie Guidez  8 , Mohamad Mohty  9 , Rene-Olivier Casasnovas  10 , Magalie Joris  11 , Cristina Castilla-Llorente  12 , Corinne Haioun  13 , Olivier Hermine  14 , Michael Loschi  15 , Sylvain Carras  16 , Pierre Bories  17 , Tom Fradon  18 , Charles Herbaux  3 , Pierre Sesques  2 , Steven Le Gouill  19 , Franck Morschhauser  4 , Catherine Thieblemont  6 , Roch Houot  1
Affiliations

Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry

Jean Lemoine et al. Blood Adv. .

Abstract

CD19 chimeric antigen receptor (CAR) T cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory large B-cell lymphomas. However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the nonrelapse mortality (NRM) after CAR T-cell therapy. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM and identified risk factors of NRM. We report on 957 patients who received standard-of-care axicabtagene ciloleucel (n = 598) or tisagenlecleucel (n = 359) between July 2018 and April 2022, in 27 French centers. With a median follow-up of 12.4 months, overall NRM occurred in 48 patients (5.0% of all patients): early (before day 28 after infusion) in 9 patients (0.9% of all patients and 19% of overall NRM), and late (on/after day 28 after infusion) in 39 patients (4.1% of all patients and 81% of overall NRM). Causes of overall NRM were distributed as follows: 56% infections (29% with non-COVID-19 and 27% with COVID-19), 10% cytokine release syndromes, 6% stroke, 6% cerebral hemorrhage, 6% second malignancies, 4% immune effector cell associated neurotoxicities, and 10% deaths from other causes. We report risk factors of early NRM and overall NRM. In multivariate analysis, both diabetes and elevated ferritin level at lymphodepletion were associated with an increased risk of overall NRM. Our results may help physicians in patient selection and management in order to reduce the NRM after CAR T-cell therapy.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: E.B. received honoraria from Kite, a Gilead Company, and Novartis. G.C. received honoraria from Kite, a Gilead Company, and Novartis. T.G. received honoraria from Kite, a Gilead Company. R.D.B. received honoraria from Kite, a Gilead Company, and Novartis. S.G. received honoraria from Kite/Gilead, Incyte, Takeda, and Janssen. M.M. received honoraria from Kite, a Gilead Company, and Novartis. R.-O.C. received honoraria from Kite, a Gilead Company. C.C.-L. received honoraria from Kite, a Gilead Company. M.L. received honoraria from Kite, a Gilead Company, and Novartis. S.L.G. reports consultancy for Kite, a Gilead Company, and Novartis. C.T. received honoraria from Kite, a Gilead Company, and Novartis. R.H. received honoraria from Kite, a Gilead Company, and Novartis. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flowchart of patient outcome (N = 957).
Figure 2.
Figure 2.
Outcomes of the entire cohort of patients treated with commercial axi-cel or tisacel from the French DESCAR-T registry. (Left) Absolute number contribution to patient outcomes (N = 957). (Right) Proportion of early and late NRM among overall NRM. Early NRM is defined by NRM occurring before day 28 after CAR T-cell injection; late NRM is defined by NRM occurring beyond day 28 after CAR T-cell injection.
Figure 3.
Figure 3.
Causes of death in the NRM population.
Figure 4.
Figure 4.
Cumulative incidence of total NRM and NRM according to the cause of death in the entire population (N = 957). (A) Cumulative incidence of NRM in the overall population (N = 957). (B) Cumulative incidence of NRM based on the cause of death.
See this image and copyright information in PMC

References

    1. 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. - PMC - PubMed
    1. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45–56. - PubMed
    1. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet Lond Engl. 2020;396(10254):839–852. - PubMed
    1. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640–654. - PubMed
    1. Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294–2308. - PubMed

Publication types

MeSH terms