Invasive Fungal Infections After Anti-CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy: State of the Evidence and Future Directions

Overview

Journal J Fungi (Basel)

Date 2021 Mar 6

PMID 33672208

Citations 17

Authors

Will Garner

Palash Samanta

Ghady Haidar

Affiliations

Soon will be listed here.

Abstract

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes.

Citing Articles

Invasive Fungal Disease After Chimeric Antigen Receptor-T Immunotherapy in Adult and Pediatric Patients.

Evangelidis P, Tragiannidis K, Vyzantiadis A, Evangelidis N, Kalmoukos P, Vyzantiadis T Pathogens. 2025; 14(2).

PMID: 40005545 PMC: 11858289. DOI: 10.3390/pathogens14020170.

Clinical Mycology Today: Emerging Challenges and Opportunities.

Little J, Rauseo A, Zuniga-Moya J, Spec A, Pappas P, Perfect J Open Forum Infect Dis. 2024; 11(7):ofae363.

PMID: 39045011 PMC: 11263878. DOI: 10.1093/ofid/ofae363.

Overview of infectious complications among CAR T- cell therapy recipients.

Arya S, Shahid Z Front Oncol. 2024; 14:1398078.

PMID: 39026972 PMC: 11255439. DOI: 10.3389/fonc.2024.1398078.

Essentials of CAR-T Therapy and Associated Microbial Challenges in Long Run Immunotherapy.

Kalim M, Jing R, Li X, Jiang Z, Zheng N, Wang Z J Cell Immunol. 2024; 6(1):22-50.

PMID: 38883270 PMC: 11172397. DOI: 10.33696/immunology.6.189.

, and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center.

Ledoux M, Dicop E, Sabou M, Letscher-Bru V, Castelain V, Danion F J Fungi (Basel). 2024; 10(4).

PMID: 38667960 PMC: 11051493. DOI: 10.3390/jof10040289.

References

Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E . Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis. 2005; 41(9):1242-50. DOI: 10.1086/496927. View

Cornely O, Maertens J, Winston D, Perfect J, Ullmann A, Walsh T . Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007; 356(4):348-59. DOI: 10.1056/NEJMoa061094. View

Maertens J, Girmenia C, Bruggemann R, Duarte R, Kibbler C, Ljungman P . European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia. J Antimicrob Chemother. 2018; 73(12):3221-3230. DOI: 10.1093/jac/dky286. View

Haidar G, Nguyen M, Samanta P . Reply to Lewis and Kontoyiannis. Clin Infect Dis. 2020; 71(7):1803-1804. DOI: 10.1093/cid/ciaa032. View

Ullmann A, Lipton J, Vesole D, Chandrasekar P, Langston A, Tarantolo S . Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007; 356(4):335-47. DOI: 10.1056/NEJMoa061098. View

Mahadeo K, Khazal S, Abdel-Azim H, Fitzgerald J, Taraseviciute A, Bollard C . Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy. Nat Rev Clin Oncol. 2018; 16(1):45-63. PMC: 7096894. DOI: 10.1038/s41571-018-0075-2. View

Vora S, Waghmare A, Englund J, Qu P, Gardner R, Hill J . Infectious Complications Following CD19 Chimeric Antigen Receptor T-cell Therapy for Children, Adolescents, and Young Adults. Open Forum Infect Dis. 2020; 7(5):ofaa121. PMC: 7221263. DOI: 10.1093/ofid/ofaa121. View

Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B . The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006; 91(8):1068-75. View

Tisi M, Hohaus S, Cuccaro A, Innocenti I, De Carolis E, Za T . Invasive fungal infections in chronic lymphoproliferative disorders: a monocentric retrospective study. Haematologica. 2016; 102(3):e108-e111. PMC: 5394967. DOI: 10.3324/haematol.2016.151837. View

10.

Garcia-Vidal C, Upton A, Kirby K, Marr K . Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis. 2008; 47(8):1041-50. PMC: 2668264. DOI: 10.1086/591969. View

11.

Los-Arcos I, Iacoboni G, Aguilar-Guisado M, Alsina-Manrique L, Diaz de Heredia C, Fortuny-Guasch C . Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper. Infection. 2020; 49(2):215-231. PMC: 7518951. DOI: 10.1007/s15010-020-01521-5. View

12.

Wudhikarn K, Palomba M, Pennisi M, Garcia-Recio M, Flynn J, Devlin S . Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma. Blood Cancer J. 2020; 10(8):79. PMC: 7405315. DOI: 10.1038/s41408-020-00346-7. View

13.

Wingard J, Leather H . Empiric antifungal therapy for the neutropenic patient. Oncology (Williston Park). 2001; 15(3):351-63; discussion 363-4, 367-9. View

14.

Yakoub-Agha I, Chabannon C, Bader P, Basak G, Bonig H, Ciceri F . Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica. 2019; 105(2):297-316. PMC: 7012497. DOI: 10.3324/haematol.2019.229781. View

15.

Maude S, Laetsch T, Buechner J, Rives S, Boyer M, Bittencourt H . Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018; 378(5):439-448. PMC: 5996391. DOI: 10.1056/NEJMoa1709866. View

16.

Pagano L, Akova M, Dimopoulos G, Herbrecht R, Drgona L, Blijlevens N . Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients. J Antimicrob Chemother. 2010; 66 Suppl 1:i5-14. DOI: 10.1093/jac/dkq437. View

17.

Schiff M, Kremer J, Jahreis A, Vernon E, Isaacs J, van Vollenhoven R . Integrated safety in tocilizumab clinical trials. Arthritis Res Ther. 2011; 13(5):R141. PMC: 3308069. DOI: 10.1186/ar3455. View

18.

Fried S, Avigdor A, Bielorai B, Meir A, Besser M, Schachter J . Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019; 54(10):1643-1650. DOI: 10.1038/s41409-019-0487-3. View

19.

Hill J, Seo S . How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood. 2020; 136(8):925-935. PMC: 7441168. DOI: 10.1182/blood.2019004000. View

20.

June C, Sadelain M . Chimeric Antigen Receptor Therapy. N Engl J Med. 2018; 379(1):64-73. PMC: 7433347. DOI: 10.1056/NEJMra1706169. View