Micafungin as primary antifungal prophylaxis in patients presenting with acute myeloid leukemia

Venton, Geoffroy; Adam, Hélène; Colle, Julien; Labiad, Yasmine; Mercier, Cédric; Ivanov, Vadim; Suchon, Pierre; Fanciullino, Raphaëlle; Farnault, Laure; Costello, Régis

doi:10.1016/j.medmal.2016.03.008

Cited by 7 publications

(5 citation statements)

References 15 publications

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“… 4 Clinical use of PCZ is nonetheless complicated by AEs, such as liver toxicity, gastrointestinal intolerance, and risk of prolonged cardiac repolarization (long QTc), especially when patients present at treatment with co‐existing risk factors or PCZ engages in PK interactions with CYP3A4 substrates that prolong QTc. 18 Micafungin shows a better safety profile than PCZ and was effective in preventing IFIs in at‐risk hematologic patients; however, the evidence derived from small single‐center retrospective or observational studies, 19 , 20 or prospective single arm interventional studies. 21 Guidelines do not therefore recommend micafungin for primary antifungal prophylaxis in patients with AML (grade C‐II evidence).…”

Section: Discussionmentioning

confidence: 99%

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Menna

Marchesi

Cattaneo

et al. 2023

Clinical Translational Sci

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Midostaurin is used in combination with chemotherapy to treat patients with newly diagnosed FLT3‐mutated acute myeloid leukemia. Chemotherapy‐induced neutropenia exposes these patients to a significant risk of invasive fungal infections (IFIs). International guidelines recommend primary antifungal prophylaxis with posaconazole (PCZ) but nested analysis of a phase III trial showed that strong PCZ inhibition of CYP3A4 diminished midostaurin metabolism and increased midostaurin plasma levels; however, midostaurin‐related adverse events (AEs) were only moderately exacerbated. We conducted a prospective multicenter real‐life study to evaluate (i) how often concerns around PCZ‐midostaurin interactions made the hematologist prescribe antifungals other than PCZ, (ii) how remarkably PCZ increased midostaurin plasma levels, and (iii) how significantly PCZ‐midostaurin interactions influenced hematologic and safety outcomes of induction therapy. Although the hematologists were blinded to pharmacokinetic findings, as many as 16 of 35 evaluable patients were prescribed antifungal prophylaxis with micafungin, weak CYP3A4 inhibitor, in place of PCZ (p < 0.001 for deviation from guidelines). In the 19 patients managed as per guidelines, PCZ‐midostaurin interactions were more remarkable than previously characterized, such that at the end of induction therapy midostaurin minimum plasma concentration (Cmin) was greater than three times higher than reported; moreover, midostaurin Cmin, maximum plasma concentration, and area under the curve were more than or equal to four times higher with PCZ than micafungin. Hematologic outcomes (complete remission and duration of severe neutropenia) and safety outcomes (midostaurin‐related any grade or grade ≥3 AEs) were nonetheless similar for patients exposed to PCZ or micafungin, as was the number of breakthrough IFIs. In waiting for randomized phase III trials of new prophylaxis regimens, these findings show that PCZ should remain the antifungal of choice for the midostaurin‐treated patient.

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Section: Discussionmentioning

confidence: 99%

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Menna

Marchesi

Cattaneo

et al. 2023

Clinical Translational Sci

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“…The prospective trial included patients undergoing RIC for AML who received micafungin once daily from the first day of induction therapy until the end of neutropenia. 59 None of the 41 patients developed bIFD. Further retrospective studies in the transplant setting confirmed these findings in larger sample sizes (ranging from 69 to 216 included patients).…”

Section: Micafunginmentioning

confidence: 94%

“…Several retrospective studies 53–58 in the transplant setting (allogeneic HSCT and SOT) as well as one prospective clinical trial 59 assessing micafungin prophylaxis in the non-transplant setting have been published since the last update of the guideline. The prospective trial included patients undergoing RIC for AML who received micafungin once daily from the first day of induction therapy until the end of neutropenia.…”

Section: Micafunginmentioning

confidence: 99%

Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Stemler

Mellinghoff

Khodamoradi

et al. 2023

Journal of Antimicrobial Chemotherapy

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Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug–drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.

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“…This is why there are consensus-based documents that point to the advantages of this drug in prophylaxis [16]. There is published experience with micafungin in the primary prophylaxis of haematological patients in the context of haematopoietic stem cell transplant and acute myeloid leukaemias induction therapy [17,18]. International guidelines provide a recommendation for micafungin, both in prophylaxis and in the treatment of the candidiasis [4,[19][20][21] Some Spanish centres have accumulated experience in primary prophylaxis with micafungin in patients admitted to haematology departments undergoing chemotherapy in whom a prolonged period of neutropenia is expected and in whom azoles might constitute a problem of tolerability due to drug interactions, liver alterations, long QT syndrome or intolerance.…”

Section: Introductionmentioning

confidence: 99%

Micafungin as antifungal prophylaxis in non-transplanted haemotological patients

Villaescusa

Vázquez²,

Bergua³

et al. 2020

Rev Esp Quimioter

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Micafungina como profilaxis antifúngica en pacientes hematológicos no trasplantados RESUMENIntroducción. Las infecciones fúngicas son una importante causa de morbilidad y mortalidad en los pacientes hematológicos. Estas infecciones son principalmente debidas a Candida spp.y Aspergillus spp. La mortalidad debida a estas infecciones es alta, pero ha descendido a lo largo de las últimas series gracias a los mejores agentes antifúngicos. Las equinocandinas son, in vitro, muy activas contra Candida y Aspergillus spp. El objetivo de este estudio es analizar la eficacia y seguridad de micafungina en la profilaxis antifúngica de pacientes hematológicos en tratamiento quimioterápico.Material y métodos. Un estudio multicéntrico, observacional, retrospectivo se llevó a cabo en 7 servicios de Hematología en España. Se incluyeron los pacientes ingresados con quimioterapia o tratamiento inmunosupresor que hubieran recibido micafunfina como profilaxis entre el 1 de enero de 2009 y el 31 de diciembre de 2014.Resultados. Hubo 5 casos de infección fúngica probable o probada (4,8%) según los criterios de la EORTC de 2008: 2 probadas, 3 probables. Las infecciones fúngicas fueron 3 aspergilosis y 2 candidiasis. No hubo ningún abandono de la profilaxis con micafungina debido a toxicidad.Conclusión. Micafungina es un agente antifúngico que, usado en profilaxis, ha demostrado buena eficacia y excelente perfil de toxicidad, siendo una opción interesante en pacientes que requieren profilaxis antifúngica durante su hospitalización. ABSTRACTIntroduction. Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocandins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haematological patients on chemotherapy.Material and methods. A multicentre, observational retrospective study was performed in 7 Haematology Departments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included.Results. There were 5 cases of probable or proven fungal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 aspergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity.Conclusion. Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode.

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Micafungin as primary antifungal prophylaxis in patients presenting with acute myeloid leukemia

Cited by 7 publications

References 15 publications

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Posaconazole and midostaurin in patients with FLT3‐mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Micafungin as antifungal prophylaxis in non-transplanted haemotological patients

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