Invasive aspergillosis in patients with acute myeloid leukemia: difficulties in choosing first-line therapy in real clinical practice and pharmacoeconomic analysis of the feasibility of using new antifungal drugs
https://doi.org/10.17650/1818-8346-2025-20-2-126-137
Abstract
The article discusses the epidemiology and difficulties of diagnosing invasive aspergillosis in patients with acute myeloid leukemia, the role of pharmacokinetic and pharmacogenetic studies in choosing the optimal treatment regimen, and an attempt at pharmacoeconomic analysis to create an optimal treatment strategy for this complication.
About the Authors
Yu. S. Osipov
V.A. Almazov National Medical Research Centre, Ministry of Health of Russia
Russian Federation
Russian Federation
Yuriy Sergeevich Osipov
2 Akkuratova St., Saint Petersburg 197341
A. A. Antonov
R-Health Consult
Russian Federation
Russian Federation
Artem Alekseevich Antonov
Build. 2, 11 Timura Frunze St., Moscow 119034
V. V. Ivanov
V.A. Almazov National Medical Research Centre, Ministry of Health of Russia
Russian Federation
Russian Federation
2 Akkuratova St., Saint Petersburg 197341
G. N. Salogub
V.A. Almazov National Medical Research Centre, Ministry of Health of Russia
Russian Federation
Russian Federation
2 Akkuratova St., Saint Petersburg 197341
References
1. Nganthavee V., Phutthasakda W., Atipas K. et al. High incidence of invasive fungal infection during acute myeloid leukemia treatment in a resource-limited country: clinical risk factors and treatment outcomes [published correction appears in Support Care Cancer 2019;27(9):3623]. Support Care Cancer 2019;27(9):3613–22. DOI: 10.1007/s00520-019-04720-5
2. Klyasova G.A., Okhmat V.A., Vasilyeva V.A. et al. Invasive mycoses in patients with acute leukemia and in recipients of hematopoietic stem cells. Results of a multicenter prospective observational study in Russia (RIFI). Gematologiya i transfuziologiya = Hematology and Transfusiology 2016;61(1–S1):19. (In Russ.).
3. 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 Infect Dis 2022;9(10):ofac486. DOI: 10.1093/ofid/ofac486
4. Wang S.T., Chou C.H., Chen T.T. et al. High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia. Front Cell Infect Microbiol 2022;12:1012334. DOI: 10.3389/fcimb.2022.1012334
5. Maertens J.A., Raad II, Marr K.A. et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet 2016;387(10020):760–9. DOI: 10.1016/S0140-6736(15)01159-9
6. Tissot F., Agrawal S., Pagano L. et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017;102(3):433–44. DOI: 10.3324/haematol.2016.152900
7. Ullmann A.J., Aguado J.M., Arikan-Akdagli S. et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect 2018;24(Suppl 1):e1–38. DOI: 10.1016/j.cmi.2018.01.002
8. Fadhel M., Patel S.V., Liu E. et al. Disseminated pulmonary with isolated muscular mucormycosis in an acute myeloid leukemia patient: a case report and literature review. Am J Case Rep 2019;20:1210–5. DOI: 10.12659/AJCR.916864
9. Klimko N.N., Khostelidi S.N., Shadrivova O.V. et al. Mucormycosis in oncohematology patients (results of the prospective study). Onkogematologiya = Oncohematology 2017;12(2):14–22. (In Russ.). DOI: 10.17650/1818-8346-2017-12-2-14-22
10. Marty F.M., Ostrosky-Zeichner L., Cornely O.A. et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis 2016;16(7):828–37. DOI: 10.1016/S1473-3099(16)00071-2
11. Malhotra S., Kumari R., Chauhan A.K. et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid sample from suspected patients of invasive pulmonary aspergillosis. Indian J Pathol Microbiol 2021;64(4):732–4. DOI: 10.4103/IJPM.IJPM_985_20
12. Guegan H., Robert-Gangneux F., Camus C. et al. Improving the diagnosis of invasive aspergillosis by the detection of Aspergillus in broncho-alveolar lavage fluid: comparison of non-culture-based assays. J Infect 2018;76(2):196–205. DOI: 10.1016/j.jinf.2017.11.011
13. Shadrivova O.V., Khostelidi S.N., Shagdileva E.V. et al. Mucormycosis and invasive aspergillosis in patients with oncohematological pathology in Russia (results of a multicenter study). Problemy meditsinskoy mikologii = Problems in Medical Mycology 2024;26(2):26–37. (In Russ.). DOI: 10.24412/1999-6780-2024-2-26-37
14. Markelov V.V., Rogacheva Yu.A., Popova M.O. et al. Invasive aspergillosis caused by Aspergillus non-fumigatus after allogeneic hematopoietic stem cell transplantation. Zhurnal infectologii = Journal Infectology 2022;14(5):5–13. (In Russ.). DOI: 10.22625/2072-6732-2022-14-5-5-13
15. Wang Y., Zhang L., Zhou L. et al. Epidemiology, drug susceptibility, and clinical risk factors in patients with invasive aspergillosis. Front Public Health 2022;10:835092. DOI: 10.3389/fpubh.2022.835092
16. Son H.J., Song J.S., Choi S. et al. A comparison of histomorphologic diagnosis with culture and immunohistochemistry-based diagnosis of invasive aspergillosis and mucormycosis. Infect Dis (London) 2020;52(4):279–83. DOI: 10.1080/23744235.2020.1716063
17. Sangoi A.R., Rogers W.M., Longacre T.A. et al. Challenges and pitfalls of morphologic identification of fungal infections in histologic and cytologic specimens: a ten-year retrospective review at a single institution. Am J Clin Pathol 2009;131(3):364–75. DOI: 10.1309/AJCP99OOOZSNISCZ
18. Guarner J., Brandt M.E. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev 2011;24(2):247–80. DOI: 10.1128/CMR.00053-10
19. Klimko N., Khostelidi S., Shadrivova O. et al. Contrasts between mucormycosis and aspergillosis in oncohematological patients. Med Mycol 2019;57(Supplement_2):S138–44. DOI: 10.1093/mmy/myy116
20. Alexander B.D., Lamoth F., Heussel C.P. et al. Guidance on imaging for invasive pulmonary aspergillosis and mucormycosis: from the imaging working group for the revision and update of the consensus definitions of fungal disease from the EORTC/ MSGERC. Clin Infect Dis 2021;72(Suppl 2):S79–88. DOI: 10.1093/cid/ciaa1855
21. Lewis R.E., Stanzani M., Morana G., Sassi C. Radiology-based diagnosis of fungal pulmonary infections in high-risk hematology patients: are we making progress? Curr Opin Infect Dis 2023;36(4):250–6. DOI: 10.1097/QCO.0000000000000937
22. Murray J., Lu Z.A., Miller K. et al. Dual disseminated aspergillosis and mucormycosis diagnosed at autopsy: a report of two cases of coinfection and a review of the literature. J Fungi (Basel) 2023;9(3):357. DOI: 10.3390/jof9030357
23. Shadrivova O.V., Khostelidi S.N., Borzova Yu.V. et al. Combination of invasive aspergillosis and mucormycosis in oncohematological patients. Onkogematologiya = Oncohematology 2017;12(4):8–17. (In Russ.). DOI: 10.17650/1818-8346-2017-12-4-8-17
24. Chamilos G., Lewis R.E., Kontoyiannis D.P. et al. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis 2008;47(4):503–9. DOI: 10.1086/590004
25. Fakhim H., Badali H., Dannaoui E. et al. Trends in the prevalence of amphotericin B-resistance (AmBR) among clinical isolates of Aspergillus species. J Mycol Med 2022;32(4):101310. DOI: 10.1016/j.mycmed.2022.101310
26. De Francesco M.A. Drug-resistant Aspergillus spp.: a literature review of its resistance mechanisms and its prevalence in Europe. Pathogens 2023;12(11):1305. DOI: 10.3390/pathogens12111305
27. Klyasova G.A. Novel treatment possibilities of invasive aspergillosis. Onkogematologiya = Oncohematology 2021;16(4):31–9. (In Russ.). DOI: 10.17650/1818-8346-2021-16-4-31-39
28. Imbert S., Portejoie L., Pfister E. et al. A multiplex PCR and DNA-sequencing workflow on serum for the diagnosis and species identification for invasive aspergillosis and mucormycosis. J Clin Microbiol 2023;61(1):e0140922. DOI: 10.1128/jcm.01409-22
29. Li X., Hu Q., Xu T. Associated factors with voriconazole plasma concentration: a systematic review and meta-analysis. Front Pharmacol 2024;15:1368274. DOI: 10.3389/fphar.2024.1368274
30. Danion F., Jullien V., Rouzaud C. et al. Is it time for systematic voriconazole pharmacogenomic investigation for central nervous system aspergillosis? Antimicrob Agents Chemother 2018;62(9):e00705–18. DOI: 10.1128/AAC.00705-18
31. Mirzaev K.B., Zelenskaya E.M., Barbarash O.L. et al. CYP2C19 polymorphism frequency in Russian patients in Central Russia and Siberia with acute coronary syndrome. Pharmgenomics Pers Med 2017;10:107–14. DOI: 10.2147/PGPM.S126305
32. Moriyama B., Obeng A.O., Barbarino J. et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2C19 and voriconazole therapy. Clin Pharmacol Ther 2017;102(1):45–51. DOI: 10.1002/cpt.953
33. Blanco-Dorado S., Maroñas O., Latorre-Pellicer A. Impact of CYP2C19 genotype and drug interactions on voriconazole plasma concentrations: a Spain pharmacogenetic-pharmacokinetic prospective multicenter study. Pharmacotherapy 2020;40(1):17–25. DOI: 10.1002/phar.2351
34. Kaindl T., Andes D., Engelhardt M. et al. Variability and exposure- response relationships of isavuconazole plasma concentrations in the Phase 3 SECURE trial of patients with invasive mould diseases. J Antimicrob Chemother 2019;74(3):761–7. DOI: 10.1093/jac/dky463
35. Vergidis P., Sendi P., Alkhateeb H.B., Nguyen M.H. How do I manage refractory invasive pulmonary aspergillosis. Clin Microbiol Infect 2024;30(6):755–61. DOI: 10.1016/j.cmi.2024.01.015
36. Donnelly J.P., Chen S.C., Kauffman C.A. et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 2020;71(6):1367–76. DOI: 10.1093/cid/ciz1008
37. Floros L., Pagliuca A., Taie A.A. et al. The cost-effectiveness of isavuconazole compared to the standard of care in the treatment of patients with invasive fungal infection prior to differential pathogen diagnosis in the United Kingdom. J Med Econ 2020;23(1):86–97. DOI: 10.1080/13696998.2019.1638789
38. Floros L., Kuessner D., Posthumus J. et al. Cost-effectiveness analysis of isavuconazole versus voriconazole for the treatment of patients with possible invasive aspergillosis in Sweden. BMC Infect Dis 2019;19(1):134. DOI: 10.1186/s12879-019-3683-2
39. Maertens J.A., Girmenia C., Brüggemann R.J. et al. 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):3221–30. DOI: 10.1093/jac/dky286
40. Vallejo C., Jarque I., Fortun J. et al. IFISTRATEGY: Spanish national survey of invasive fungal infection in hemato-oncologic patients. J Fungi 2023;9(6):628. DOI: 10.3390/jof9060628
41. Naser A., Bilbisi M., Mousa R. EE487 cost-effectiveness analysis of isavuconazole versus liposomal amphotericin for the treatment of invasive mucormycosis in Jordan. Value in Health 2023;26(12):S145.
42. Alqarihi A., Kontoyiannis D.P., Ibrahim A.S. Mucormycosis in 2023: an update on pathogenesis and management. Front Cell Infect Microbiol 2023;13:1254919. DOI: 10.3389/fcimb.2023.1254919
43. Petrikkos G.L. Lipid formulations of amphotericin B as first line treatment of zygomycosis. Clin Microbiol Infect 2009;15 Suppl 5: 87–92. DOI: 10.1111/j.1469-0691.2009.02987.x
44. Popova M.O., Rogacheva Yu.A. Mucormycosis: modern diagnostics and treatment, existing problems and new trends in antifungal therapy. Klinicheskaya mikrobiologiya i antimicrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy. 2021;23(3):226–38. (In Russ.). DOI: 10.36488/cmac.2021.3.226-238
Review
For citations:
Osipov Yu.S., Antonov A.A., Ivanov V.V., Salogub G.N. Invasive aspergillosis in patients with acute myeloid leukemia: difficulties in choosing first-line therapy in real clinical practice and pharmacoeconomic analysis of the feasibility of using new antifungal drugs. Oncohematology. 2025;20(2):126-137. (In Russ.) https://doi.org/10.17650/1818-8346-2025-20-2-126-137
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