Empiric vs Preemptive Antifungal Strategy in High-Risk
Neutropenic Patients on Fluconazole Prophylaxis: A Randomized
Trial of the European Organization for Research and Treatment
of Cancer

J 2023

Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer

MAERTENS, Johan, Tom LODEWYCK, J Peter DONNELLY, Sylvain CHANTEPIE, Christine ROBIN et. al.

Basic information

Original name

Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer

Authors

MAERTENS, Johan (guarantor), Tom LODEWYCK, J Peter DONNELLY, Sylvain CHANTEPIE, Christine ROBIN, Nicole BLIJLEVENS, Pascal TURLURE, Dominik SELLESLAG, Frederic BARON, Mickael AOUN, Werner J HEINZ, Hartmut BERTZ, Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), Bernard VANDERCAM, Lubos DRGONA, Valerie COITEUX, Cristina Castilla LLORENTE, Cornelia SCHAEFER-PROKOP, Marianne PAESMANS, Lieveke AMEYE, Liv MEERT, Kin Jip CHEUNG, Deborah A HEPLER, Juergen LOEFFLER, Rosemary BARNES, Oscar MARCHETTI, Paul VERWEIJ, Frederic LAMOTH, Pierre-Yves BOCHUD, Michael SCHWARZINGER and Catherine CORDONNIER

Edition

Clinical Infectious Diseases, CARY, OXFORD UNIV PRESS INC, 2023, 1058-4838

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 11.800 in 2022

RIV identification code

RIV/00216224:14110/23:00130259

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1093/cid/ciac623

UT WoS

000843548400001

Keywords in English

neutropenia; empiric; preemptive; antifungal; galactomannan

Abstract

V originále

The initiation of antifungal therapy with caspofungin based on serum galactomannan screening and computed tomography scan when required in profound and prolonged neutropenic patients given fluconazole prophylaxis was found to be noninferior to a fever-driven empiric approach. Background Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. Methods Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. Results Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). Conclusions The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.

Citovat

MAERTENS, Johan, Tom LODEWYCK, J Peter DONNELLY, Sylvain CHANTEPIE, Christine ROBIN, Nicole BLIJLEVENS, Pascal TURLURE, Dominik SELLESLAG, Frederic BARON, Mickael AOUN, Werner J HEINZ, Hartmut BERTZ, Zdeněk RÁČIL, Bernard VANDERCAM, Lubos DRGONA, Valerie COITEUX, Cristina Castilla LLORENTE, Cornelia SCHAEFER-PROKOP, Marianne PAESMANS, Lieveke AMEYE, Liv MEERT, Kin Jip CHEUNG, Deborah A HEPLER, Juergen LOEFFLER, Rosemary BARNES, Oscar MARCHETTI, Paul VERWEIJ, Frederic LAMOTH, Pierre-Yves BOCHUD, Michael SCHWARZINGER and Catherine CORDONNIER. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clinical Infectious Diseases. CARY: OXFORD UNIV PRESS INC, 2023, vol. 76, No 4, p. 674-682. ISSN 1058-4838. Available from: https://dx.doi.org/10.1093/cid/ciac623.

@article{2251446,
   author = {Maertens, Johan and Lodewyck, Tom and Donnelly, J Peter and Chantepie, Sylvain and Robin, Christine and Blijlevens, Nicole and Turlure, Pascal and Selleslag, Dominik and Baron, Frederic and Aoun, Mickael and Heinz, Werner J and Bertz, Hartmut and Ráčil, Zdeněk and Vandercam, Bernard and Drgona, Lubos and Coiteux, Valerie and Llorente, Cristina Castilla and SchaeferandProkop, Cornelia and Paesmans, Marianne and Ameye, Lieveke and Meert, Liv and Cheung, Kin Jip and Hepler, Deborah A and Loeffler, Juergen and Barnes, Rosemary and Marchetti, Oscar and Verweij, Paul and Lamoth, Frederic and Bochud, PierreandYves and Schwarzinger, Michael and Cordonnier, Catherine},
   article_location = {CARY},
   article_number = {4},
   doi = {http://dx.doi.org/10.1093/cid/ciac623},
   keywords = {neutropenia; empiric; preemptive; antifungal; galactomannan},
   language = {eng},
   issn = {1058-4838},
   journal = {Clinical Infectious Diseases},
   title = {Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer},
   url = {https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac623/6652161?login=true},
   volume = {76},
   year = {2023}
}

TY  - JOUR
ID  - 2251446
AU  - Maertens, Johan - Lodewyck, Tom - Donnelly, J Peter - Chantepie, Sylvain - Robin, Christine - Blijlevens, Nicole - Turlure, Pascal - Selleslag, Dominik - Baron, Frederic - Aoun, Mickael - Heinz, Werner J - Bertz, Hartmut - Ráčil, Zdeněk - Vandercam, Bernard - Drgona, Lubos - Coiteux, Valerie - Llorente, Cristina Castilla - Schaefer-Prokop, Cornelia - Paesmans, Marianne - Ameye, Lieveke - Meert, Liv - Cheung, Kin Jip - Hepler, Deborah A - Loeffler, Juergen - Barnes, Rosemary - Marchetti, Oscar - Verweij, Paul - Lamoth, Frederic - Bochud, Pierre-Yves - Schwarzinger, Michael - Cordonnier, Catherine
PY  - 2023
TI  - Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer
JF  - Clinical Infectious Diseases
VL  - 76
IS  - 4
SP  - 674-682
EP  - 674-682
PB  - OXFORD UNIV PRESS INC
SN  - 10584838
KW  - neutropenia
KW  - empiric
KW  - preemptive
KW  - antifungal
KW  - galactomannan
UR  - https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac623/6652161?login=true
N2  - The initiation of antifungal therapy with caspofungin based on serum galactomannan screening and computed tomography scan when required in profound and prolonged neutropenic patients given fluconazole prophylaxis was found to be noninferior to a fever-driven empiric approach. Background Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. Methods Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. Results Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). Conclusions The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.
ER  -

MAERTENS, Johan, Tom LODEWYCK, J Peter DONNELLY, Sylvain CHANTEPIE, Christine ROBIN, Nicole BLIJLEVENS, Pascal TURLURE, Dominik SELLESLAG, Frederic BARON, Mickael AOUN, Werner J HEINZ, Hartmut BERTZ, Zdeněk RÁČIL, Bernard VANDERCAM, Lubos DRGONA, Valerie COITEUX, Cristina Castilla LLORENTE, Cornelia SCHAEFER-PROKOP, Marianne PAESMANS, Lieveke AMEYE, Liv MEERT, Kin Jip CHEUNG, Deborah A HEPLER, Juergen LOEFFLER, Rosemary BARNES, Oscar MARCHETTI, Paul VERWEIJ, Frederic LAMOTH, Pierre-Yves BOCHUD, Michael SCHWARZINGER and Catherine CORDONNIER. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. \textit{Clinical Infectious Diseases}. CARY: OXFORD UNIV PRESS INC, 2023, vol.~76, No~4, p.~674-682. ISSN~1058-4838. Available from: https://dx.doi.org/10.1093/cid/ciac623.

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