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Antifungal prophylaxis in patients with acute myeloid leukaemia treated with venetoclax and azacitidine


Authors: B. Weinbergerová
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno
Published in: Transfuze Hematol. dnes,32, 2026, No. 1, p. 28-34.
Category: Review/Educational Papers
doi: https://doi.org/10.48095/cctahd202602

Overview

Invasive fungal diseases (IFDs) represent a serious cause of morbidity and mortality in patients with acute myeloid leukaemia (AML) treated with intensive therapy, particularly following induction chemotherapy and allogeneic haematopoietic stem cell transplantation. The combination of the BCL-2 inhibitor venetoclax with the hypomethylating agent azacitidine (VEN+AZA) has become standard therapy for patients unfit for intensive chemotherapy, leading to a significant improvement in outcomes, especially when followed by allogeneic transplantation. However, this regimen may be associated with prolonged neutropenia and other factors that substantially increase the risk of IFDs. Published retrospective studies report highly variable incidences of IFDs (0.5–26%) and inconsistent effects of antifungal prophylaxis, largely due to marked heterogeneity of the evaluated cohorts, differences in the use and type of antifungal prophylaxis, definitions of IFDs, and other variables. Nevertheless, most studies have not demonstrated a significant impact of prophylaxis on the incidence of IFDs, although their purely retrospective design must be taken into account. In addition, drug–drug interactions between venetoclax and azole antifungals may pose a potential risk by increasing venetoclax toxicity. Based on currently available data, routine antifungal prophylaxis is not universally indicated, but should be considered only in defined high-risk patient groups (relapsed/refractory AML, a history of IFD, or prolonged severe neutropenia). The aim of this article was to summarise the available evidence on the efficacy and safety of antifungal prophylaxis in patients with AML treated with the VEN+AZA regimen. This review highlights the need for prospective studies and risk stratification to allow a more detailed assessment of the role of antifungal prophylaxis in this patient cohort.

Keywords:

acute myeloid leukaemia – venetoclax – azacitidine – antifungal prophylaxis


Sources

1. Elgenidy A, Al-Kurdi MA-M, Ibrahim HAA, et al. Mapping the grounds for mortalities in acute myeloid leukemia through registry analyses: a retrospective cohort study of children, adolescents, and young adult patients. J Clin Med Res. 2024; 16 (6): 310–318. doi: 10.14740/jocmr5205.

2. Logan C, Koura D, Taplitz R. Updates in infection risk and management in acute leukemia. Hematology. Am Soc Hematol Educ Prog. 2020; 1 : 135–139. doi: 10.1182/hematology. 2020000098.

3. Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. New Engl J Med. 2007; 356 (4): 348–359. doi: 10.1056/NEJMoa061094.

4. Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. New Engl J Med. 2007; 356 (4): 335–347. doi: 10.1056/NEJM oa061098.

5. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. New Engl J Med. 2020; 383 (7): 617–629. doi: 10.1056/NEJMoa 2012971.

6. Costa Passos PR, Costa Filho VO, Noronha MM, Filho CMdeO. Is antifungal prophylaxis needed for acute myeloid leukaemia patients treated with venetoclax-based regimens? A systematic review and meta-analysis. Mycoses. 2025; 68 (7): e70089. doi: 10.1111/myc.70089.

7. Aldoss I, Dadwal S, Zhang J, et al. Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents. Blood Adv. 2019; 3 (23): 4043–4049. doi: 10.1182/10.1182/bloodadvances.20190 00930.

8. On S, Rath CD, Lan M, et al. Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent. Br J Haematol. 2022; 197 : 63–70. doi: 10.1111/bjh.18051.

9. Wang S-T, Chou CH, Chen TT, et al. High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia. Front Cell Inf Microbiol. 2022; 12 : 1012334. doi: 10.3389/fcimb.2022.1012334.

10. Weinbergerová B, Mayer J, Kabut T, et al. Fungal infection frequency in newly diagnosed acute myeloid leukaemia patients treated with venetoclax plus azacitidine with or without antifungal prophylaxis. Br J Haematol. 2024; 205 (5): 1746–1750. doi: 10.1111/bjh. 19670.

11. Chen EC, Liu Y, Harris CE, et al. Outcomes of antifungal prophylaxis for newly diagnosed AML patients treated with a hypomethylating agent and venetoclax. Leuk Lymphoma. 2022; 63 : 1934–1941. doi: 10.1080/10428194. 2022.2047964.

12. DiNardo CD, Pratz K, Pullkart V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019; 133 (1): 7–17. doi: 10.1182/blood-2018-08-868752.

13. Agarwal SK, DiNardo CD, Potluri J, et al. Management of venetoclax-posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments. Clin Ther. 2017; 39 (2): 359–367. doi: 10.1016/j.clinthera.2017.01.003.

14. Zhang A, Johnson T, Abbott D, et al. Incidence of invasive fungal infections in patients with previously untreated acute myeloid leukemia receiving venetoclax and azacitidine. Open Forum Inf Dis. 2022; 9 (10): ofac486. doi: 10.1093/ofid/ofac486.

15. De la Garza-Salazar F, Colunga-Pedraza PR, Gomez-Almaguer D, Garzia-Zárate VA, Gómez-DeLeon A. Low dose venetoclax plus itraconazole outpatient induction in newly diagnosed acute myeloid leukemia: A phase 2 study. Leuk Res. 2023; 133 : 107373. doi: 10.1016/j.leukres.2023.107373.

16. Zhong X, Wang J, Huang X, et al. Combining azole antifungals with venetoclax plus azacitidine in patients with newly diagnosed acute myeloid leukemia. Hematology. 2024; 29 (1): 2433172. doi: 10.1080/16078454.2024.2433172.

17. Souhrn údajů o léčivém přípravku (Venclyxto®). [online]. Dostupné z: https: //www.ema.europa.eu/cs/documents/product-information/venclyxto-epar-product-information_cs.pdf.

18. Rausch CR, DiNardo CD, Maiti A, et al. Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia. Cancer. 2021; 127 (14): 2489–2499. doi: 10.1002/cncr.33508.

19. Zhu W, Zhu L, Hu X, et al. Safety and infection risk factors in elderly acute myeloid leukemia patients undergoing induction therapy with venetoclax combined with hypomethylating agents. Am J Cancer Res. 2024; 14 (12): 5897–5908. doi: 10.62347/VZZV6163.

20. Teh CE, Peng H, Luo M-x, et al. Venetoclax treatment in patients with cancer has limited impact on circulating T and NK cells. Blood Adv. 2023; 7 (12): 2733–2745. doi: 10.1182/ bloodadvances.2022008221.

21. Lee R, Cho S-Y, Lee D-G, et al. Infections of venetoclax-based chemotherapy in acute myeloid leukemia: rationale for proper antimicrobial prophylaxis. Cancers (Basel). 2021; 13 : 6285. doi: 10.3390/cancers13246285.

22. Stemler J, DeJong N, Skoetz M, et al. Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association. Lancet Haematol. 2022; 9: e361–e373. doi: 10.1016/S2352-3026 (22) 00073-4.

23. Lindsay J, Teh BW, Micklethwaite K, Slavin M. Azole antifungals and new targeted therapies for hematological malignancy. Curr Opin Inf Dis. 2019; 32 (6): 538–545. doi: 10.1097/QCO.000000 0000000611.

24. Pagano L, Maschmeier G, Lamoth F, et al. Primary antifungal prophylaxis in hematological malignancies. Updated clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL). Leukemia. 2025; 39 (7): 1547–1557. doi: 10.1038/s41375-025 -⁠ 02586-7.

25. Jonas BA, DiNardo CD, Fracchiolla N, et al. Use of CYP3Ai and impact on outcomes in patients with acute myeloid leukemia treated with venetoclax plus azacitidine in the VIALE-A study. Am J Hematol. 2022; 97 (11): E422–E425. doi: 10.1002/ajh.26707.

26. Hall VG, Tang K, Kumar D, et al. Breakthrough invasive fungal infection after coadministration of venetoclax and voriconazole. Open Forum Infect Dis. 2023; 10: ofad134. doi: 10.1093/ofid/ofad134.

27. Sciumè M, Bosi A, Canzi M, et al. Real-life monocentric experience of venetoclax-based regimens for acute myeloid leukemia. Front Oncol. 2023; 13 : 1149298. doi: 10.3389/fonc.2023.1149298.

28. Li P, Luo Z, Deng J. Strategies for the prophylaxis of invasive fungal diseases in acute myeloid leukemia patients undergoing Bcl-2 inhibitor venetoclax treatment. J Inf Chemother. 2025; 31 (2): 102576. doi: 10.1016/ j.jiac.2024.12.005.

29. Jonas BA, Pollyea DA. How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia. Leukemia. 2019; 33 : 2795–804.

30. Maschmeyer G, Bullinger L, Garcia-Vidal C, et al. Infectious complications of targeted drugs and biotherapies in acute leukemia. Clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN). Leukemia. 2022; 36 (5): 1215–1226. doi: 10.1038/s41375-022-01556-7.

31. Guarana M, Nucci M. Should patients with acute myeloid leukemia treated with venetoclax-based regimens receive antifungal prophylaxis? Leuk Res. 2023; 131 : 107341. doi: 10.1016/j.leukres.2023.107341.

Konflikt zájmů

V souvislosti s tématem tohoto článku byla vyplacena odměna za přednáškovou činnost od společnosti AbbVie.

Do redakce doručeno dne: 10. 11. 2025.

Přijato po recenzi dne: 2. 12. 2025.

doc. MUDr. Barbora Weinbergerová, Ph.D.

Interní hematologická a onkologická klinika

LF MU a FN Brno

Jihlavská 20

625 00 Brno Bohunice

e-mail: weinbergerova.barbora@fnbrno.cz

Labels
Haematology Internal medicine Clinical oncology

Article was published in

Transfusion and Haematology Today

Issue 1

2026 Issue 1

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