EHA Library - The official digital education library of European Hematology Association (EHA)

EHA GUIDELINE: ANTIFUNGAL PROPHYLAXIS IN ACUTE MYELOID LEUKEMIA TREATED WITH NOVEL AGENTS
Author(s): ,
Jannik Stemler
Affiliations:
Department I for Internal Medicine,University Hospital of Cologne,Cologne,Germany;Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD),University of Cologne,Cologne,Germany;Partner Site Bonn-Cologne,,German Centre for Infection Research (DZIF),Cologne,Germany
,
Nicole Skoetz
Affiliations:
Cochrane Haematology Department I of Internal Medicine,University Hospital Cologne,Cologne,Germany
,
Nick de Jonge
Affiliations:
Department of Haematology,Amsterdam UMC,Amsterdam,Netherlands
,
Roger Bruggemann
Affiliations:
Department of Clinical Pharmacy, and Nijmegen Institute for Health Sciences,Radboud University Medical Center,Nijmegen,Netherlands
,
János Sinkó
Affiliations:
Department of Hematology and HSCT,South-Pest Central Hospital National Institute of Hematology and Infectious Diseases,Budapest,Hungary
,
Alessandro Busca
Affiliations:
Dipartimento di Oncologia ed Ematologia SSCVD Trapianto allogenico di Cellule Staminali,A.O. Citta' della Salute e della Scienza di Torino,Torino,Italy
,
Zdenek Rácil
Affiliations:
Ustav Hematologie A Krevni Transfuze,Ustav Hematologie A Krevni Transfuze,Prague,Czech Republic
,
Ronen Ben Ami
Affiliations:
Infectious Diseases division, Infectious Diseases unit,Tel Aviv Sourasky Medical Center,Tel Aviv,Israel
,
Vanessa Piechotta
Affiliations:
Cochrane Haematology Department I of Internal Medicine,University Hospital of Cologne,Cologne,Germany
,
Russell Lewis
Affiliations:
Dipartimento di Scienze Mediche e Chirurgichea,Alma Mater Studiorum Università di Bologna,Bologna,Italy
Oliver Cornely
Affiliations:
Department I of Internal Medicine,University Hospital of Cologne,Cologne,Germany;Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD),University of Cologne,Cologne,Germany;German Centre for Infection Research (DZIF),Partner Site Cologne-Bonn,Cologne,Germany;Clinical Trials Centre Cologne (ZKS Köln),University of Cologne, Faculty
EHA Library. Stemler J. 06/09/21; 324689; S281
Dr. Jannik Stemler
Dr. Jannik Stemler
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S281

Type: Oral Presentation

Session title: Fungal, bacterial and viral infections in hematology

Background
Novel therapeutic agents for acute myeloid leukemia (AML) have become available recently. Antifungal prophylaxis is generally recommended during induction remission chemotherapy, however, treatment settings for AML patients have become diverse and the risk-benefit ratio for antifungal prophylaxis in those settings is not well assessed in clinical trials. Due to cytochrome p450 metabolization and its inhibition by antifungal drugs, there is potential for drug-drug interactions (DDI) between novel AML agents and antifungals.

Aims
To define evidence- or consensus-based recommendations for antifungal prophylaxis for AML patients on treatment with novel agents

Methods
Experts from the European Hematology Association (EHA) Working Group Infections in Hematology and Cochrane Hematology Group develop an evidence and consensus-based guideline according to the GRADE methodology. The following PICO endpoints for each of the novel agents were formulated: occurrence of fungal infection, prolongation of hospitalization, days on intensive-care unit and mortality due to fungal infection, quality-of-life, and potential drug-drug interactions. Systematic literature review was performed. In three consensus-meetings, recommendations for each novel AML drug and specific setting were formulated.

Results
The following novel agents for treatment of AML were identified with not all of them being yet licensed for treatment: Hypomethylating agents (HMA; Azacytidine and decitabine), Midostaurin, Venetoclax (+HMA), Lestaurtinib, Gilteritinib, Sorafenib, Quizartinib, Ivosidenib, Enasidenib, Crenolanib, Glasdegib, Sapacitabine, Custatuzumab, Iomab B, Idanasutlin.

Evidence from the literature was generally scarce since fungal infections and prophylaxis were generally not assessed in randomized controlled trials of the respective AML drug.


Evidence-based recommendations were formulated for HMA, Midostaurin, and Venetoclax/HMA, for all other agents, consensus-based recommendations were given including the patient-specific setting of application of the novel agents (relapsed/refractory AML, single therapy or in combination with chemotherapy, induction treatment or maintenance etc.) into the decision process


Antifungal prophylaxis is not recommended or moderately recommended in most settings, and strongly recommended if the novel AML agent is administered with intensive chemotherapy during induction treatment. Dose adaptations of some of the AML agents (midostaurin, venetoclax, quizartinib, sorafenib, gilteritinib) are moderately recommended with limited evidence if antifungal prophylaxis is administered with a strong CYP3A4 inhibitor due to expected increased exposure

Conclusion
This guideline document to help supporting the decision if to use antifungal prophylaxis in AML patients under treatment with novel agents will soon become available as the first one assessing this specific setting and will complement existing guidelines for antifungal prophylaxis.

Keyword(s): Acute myeloid leukemia, Drug interaction, Fungal infection, Prophylaxis

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S281

Type: Oral Presentation

Session title: Fungal, bacterial and viral infections in hematology

Background
Novel therapeutic agents for acute myeloid leukemia (AML) have become available recently. Antifungal prophylaxis is generally recommended during induction remission chemotherapy, however, treatment settings for AML patients have become diverse and the risk-benefit ratio for antifungal prophylaxis in those settings is not well assessed in clinical trials. Due to cytochrome p450 metabolization and its inhibition by antifungal drugs, there is potential for drug-drug interactions (DDI) between novel AML agents and antifungals.

Aims
To define evidence- or consensus-based recommendations for antifungal prophylaxis for AML patients on treatment with novel agents

Methods
Experts from the European Hematology Association (EHA) Working Group Infections in Hematology and Cochrane Hematology Group develop an evidence and consensus-based guideline according to the GRADE methodology. The following PICO endpoints for each of the novel agents were formulated: occurrence of fungal infection, prolongation of hospitalization, days on intensive-care unit and mortality due to fungal infection, quality-of-life, and potential drug-drug interactions. Systematic literature review was performed. In three consensus-meetings, recommendations for each novel AML drug and specific setting were formulated.

Results
The following novel agents for treatment of AML were identified with not all of them being yet licensed for treatment: Hypomethylating agents (HMA; Azacytidine and decitabine), Midostaurin, Venetoclax (+HMA), Lestaurtinib, Gilteritinib, Sorafenib, Quizartinib, Ivosidenib, Enasidenib, Crenolanib, Glasdegib, Sapacitabine, Custatuzumab, Iomab B, Idanasutlin.

Evidence from the literature was generally scarce since fungal infections and prophylaxis were generally not assessed in randomized controlled trials of the respective AML drug.


Evidence-based recommendations were formulated for HMA, Midostaurin, and Venetoclax/HMA, for all other agents, consensus-based recommendations were given including the patient-specific setting of application of the novel agents (relapsed/refractory AML, single therapy or in combination with chemotherapy, induction treatment or maintenance etc.) into the decision process


Antifungal prophylaxis is not recommended or moderately recommended in most settings, and strongly recommended if the novel AML agent is administered with intensive chemotherapy during induction treatment. Dose adaptations of some of the AML agents (midostaurin, venetoclax, quizartinib, sorafenib, gilteritinib) are moderately recommended with limited evidence if antifungal prophylaxis is administered with a strong CYP3A4 inhibitor due to expected increased exposure

Conclusion
This guideline document to help supporting the decision if to use antifungal prophylaxis in AML patients under treatment with novel agents will soon become available as the first one assessing this specific setting and will complement existing guidelines for antifungal prophylaxis.

Keyword(s): Acute myeloid leukemia, Drug interaction, Fungal infection, Prophylaxis

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies