Universität zu Köln

Stemler, Jannik ORCID: 0000-0001-9152-2469, Koehler, Philipp ORCID: 0000-0002-7386-7495, Maurer, Christian, Mueller, Carsten and Cornely, Oliver A. (2020). Antifungal prophylaxis and novel drugs in acute myeloid leukemia: the midostaurin and posaconazole dilemma. Ann. Hematol., 99 (7). S. 1429 - 1441. NEW YORK: SPRINGER. ISSN 1432-0584

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Abstract

With the advent of new targeted drugs in hematology and oncology patient prognosis is improved. Combination with antifungal prophylaxis challenges clinicians due to pharmacological profiles prone to drug-drug interactions (DDI). Midostaurin is a novel agent for FLT3-TKD/-ITDmut-acute myeloid leukemia (AML) and metabolized via cytochrome P450 3A4 (CYP3A4). Posaconazole is a standard of care antifungal agent used for prophylaxis during induction treatment of AML and a strong CYP3A4 inhibitor. Concomitant administration of both drugs leads to elevated midostaurin exposure. Both drugs improve overall survival at low numbers needed to treat. The impact of CYP3A4-related DDI remains to be determined. Severe adverse events have been observed; however, it remains unclear if they can be directly linked to DDI. The lack of prospective clinical studies assessing incidence of invasive fungal infections and clinical impact of DDI contributes to neglecting live-saving antifungal prophylaxis. Management strategies to combine both drugs have been proposed, but evidence on which approach to use is scarce. In this review, we discuss several approaches in the specific clinical setting of concomitant administration of midostaurin and posaconazole and give examples from everyday clinical practice. Therapeutic drug monitoring will become increasingly important to individualize and personalize antineoplastic concomitant and antifungal treatment in the context of DDI. Pharmaceutical companies addressing the issue in clinical trials may take a pioneer role in this field. Other recently developed and approved drugs for the treatment of AML likely inhere potential of DDI marking a foreseeable issue in future treatment of this life-threatening disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stemler, Jannik UNSPECIFIED orcid.org/0000-0001-9152-2469 UNSPECIFIED Koehler, Philipp UNSPECIFIED orcid.org/0000-0002-7386-7495 UNSPECIFIED Maurer, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-330360
DOI:	10.1007/s00277-020-04107-1
Journal or Publication Title:	Ann. Hematol.
Volume:	99
Number:	7
Page Range:	S. 1429 - 1441
Date:	2020
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0584
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INVASIVE FUNGAL-INFECTIONS; TYROSINE KINASE INHIBITOR; OPEN-LABEL; RISK-STRATIFICATION; ACTIVATING MUTATION; TABLET FORMULATION; AZOLE ANTIFUNGALS; FLT3 MUTATIONS; PHASE-I; PHARMACOKINETICS Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33036