{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:15:05Z","timestamp":1778638505600,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Midostaurin is used in combination with chemotherapy to treat patients with newly diagnosed FLT3\u2010mutated acute myeloid leukemia. Chemotherapy\u2010induced 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\u2010related adverse events (AEs) were only moderately exacerbated. We conducted a prospective multicenter real\u2010life study to evaluate (i) how often concerns around PCZ\u2010midostaurin interactions made the hematologist prescribe antifungals other than PCZ, (ii) how remarkably PCZ increased midostaurin plasma levels, and (iii) how significantly PCZ\u2010midostaurin 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 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 for deviation from guidelines). In the 19 patients managed as per guidelines, PCZ\u2010midostaurin interactions were more remarkable than previously characterized, such that at the end of induction therapy midostaurin minimum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>min<\/jats:sub>) was greater than three times higher than reported; moreover, midostaurin <jats:italic>C<\/jats:italic><jats:sub>min<\/jats:sub>, 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\u2010related any grade or grade \u22653 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\u2010treated patient.<\/jats:p>","DOI":"10.1111\/cts.13595","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T06:39:10Z","timestamp":1690612750000},"page":"1876-1885","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Posaconazole and midostaurin in patients with <scp>FLT3<\/scp>\u2010mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7755-818X","authenticated-orcid":false,"given":"Pierantonio","family":"Menna","sequence":"first","affiliation":[{"name":"University Campus Bio\u2010Medico and Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6353-2272","authenticated-orcid":false,"given":"Francesco","family":"Marchesi","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplant Unit IRCCS Regina Elena National Cancer Institute  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Azienda Socio Sanitaria Territoriale and Spedali Civili  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Candoni","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Universitaria Integrata University Hospital  Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Delia","sequence":"additional","affiliation":[{"name":"Hematology Section, Department of Emergency and Organ Transplant Univeristy of Bari  Bari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianpaolo","family":"Nadali","sequence":"additional","affiliation":[{"name":"U.O.C. 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