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
. 2024 Jul 23;8(14):3813-3822.
doi: 10.1182/bloodadvances.2024012922.

Incidence and outcomes of cytomegalovirus reactivation after chimeric antigen receptor T-cell therapy

Rick Y Lin  1 , Anthony D Anderson  2 , Yoichiro Natori  3 , Mohammed Raja  3 , Michele I Morris  3 , Antonio Jimenez Jimenez  4 , Amer Beitinjaneh  4 , Trent Wang  4 , Mark Goodman  4 , Lazaros Lekakis  4 , Jay Spiegel  4 , Noa G Holtzman  4 , Denise Pereira  4 , Cara Benjamin  4 , Akina Natori  5 , Krishna V Komanduri  6 , Jose F Camargo  3
Affiliations

Incidence and outcomes of cytomegalovirus reactivation after chimeric antigen receptor T-cell therapy

Rick Y Lin et al. Blood Adv. .

Abstract

Cytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia), and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: M.I.M received funding from Eurofins Viracor. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Increased risk of CMV reactivation in CAR T-cell therapy recipients receiving immunosuppression. (A) The 180-day incidence of CMV reactivation (any viremia) in the entire cohort. (B-G) The 180-day incidence of CMV reactivation (any viremia) by (B) degree of CRS, (C) corticosteroid use, (D) tocilizumab use, (E) use of ≥2 immunosuppressants, (F) anakinra use, and (G) degree of ICANS. The number of subjects was 94.
Figure 2.
Figure 2.
Increased risk of clinically significant CMV reactivation in CAR T-cell therapy recipients receiving immunosuppression. (A) The 180-day incidence of clinically significant CMV reactivation in the entire cohort. (B-G) The 180-day incidence of clinically significant CMV reactivation in patients receiving CAR T-cell therapy by (B) degree of CRS, (C) corticosteroid use, (D) tocilizumab use, (E) use of ≥2 immunosuppressants, (F) anakinra use, and (G) degree of ICANS. The number of subjects was 94.
Figure 3.
Figure 3.
CAR T-cell outcomes by CMV reactivation. (A) 1-year overall mortality, (B) 1-year nonrelapsed mortality, and (C) 1-year progression/relapse rates after CAR T-cell therapy among patients with no CMV reactivation and those with CMV reactivation by day 28. The number of subjects was 95.
See this image and copyright information in PMC

References

    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. 2020;396(10254):839–852. - PubMed
    1. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):1331–1342. - PMC - PubMed
    1. Rendo MJ, Joseph JJ, Phan LM, DeStefano CB. CAR T-cell therapy for patients with multiple myeloma: current evidence and challenges. Blood Lymphat Cancer. 2022;12:119–136. - PMC - PubMed
    1. Hill JA, Li D, Hay KA, et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood. 2018;131(1):121–130. - PMC - PubMed
    1. Logue JM, Zucchetti E, Bachmeier CA, et al. Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. Haematologica. 2021;106(4):978–986. - PMC - PubMed

Substances