Posaconazole at Standard Dose Is Safe and More Effective Than Echinocandins As IFD Prophylaxis in Patients with FLT3 Mutated AML Treated with Midostaurin in Blood
2021
AOU Città della Salute di Torino
Tipo pubblicazione
Conference Abstract
Autori/Collaboratori (19)Vedi tutti...
Cattaneo C
Hematology, ASST Spedali Civili di Brescia, Brescia, Italy
Marchesi F
Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute Rome, Italia, Roma, Italy
Bonuomo V
Hematology Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
et alii...
Abstract
Introduction. The potential drug-drug interactions of midostaurin (M), particularly with CYP450 inhibitors, may impact the choice of antifungal (AF) prophylaxis and treatment in FLT3-positive (FLT3+) acute myeloid leukemia (AML) patients (pts). However, there are no supportive data to guide the choice of AF drugs in this subset of pts. Aim. To evaluate the incidence of invasive fungal diseases (IFD) during induction and consolidation treatment of FLT3+ AML pts and to correlate it to the different AF prophylaxis strategies adopted. Patients and Methods. Within the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) Group, we planned a restrospective/prospective multicenter observational study enrolling all FLT3+ AML pts treated with chemotherapy (CHT)+M. IFD were classified as possible, probable and proven according to EORTC/MSG revised definitions (Donnelly JP et al, Clin Infect Dis 2020). Relationships between the type of AF prophylaxis, IFD development and AML outcome were evaluated. Results. As of 30 th June, 90 pts treated with CHT+M as induction/reinduction, consolidation or both, have been enrolled. M/F ratio was 35/55, median age 56y (range 18-78). FLT-ITD and FLT3-TKD mutations were detected in 73 and 17 pts, respectively, NPM-1 mutation in 51 (57%) pts. AML risk stratification according to ELN classification was available in 80 pts (24 low risk). A total of 216 CHT+M courses have been delivered (85 inductions, 8 reinductions and 135 consolidations). Overall, 25 IFD were reported: 19 during induction (22%), 2 during reinduction (25%) and 4 during consolidation (3%) given without AF prophylaxis in all the four. Sixty-five (72%) pts achieved complete remission (CR) after the induction. During induction, 11 pts did not receive mold-active AF prophylaxis and developed 4 (36%) IFD (3 possible and 1 probable aspergillosis), while 74 pts received mold-active AF prophylaxis and developed 15 (20%) IFD (8 possible and 4 probable aspergillosis, 3 candi
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DOI : 10.1182/blood-2021-149080
Keywords
amphotericin B; caspofungin; CD135 antigen; eculizumab; endogenous compound; isavuconazole; micafungin; midostaurin; nucleophosmin; posaconazole; adult; adverse drug reaction; advisory committee; aspergillosis; cancer chemotherapy; cancer patient; cancer survival; candidemia; clinical assessment; complication; conference abstract; controlled study; drug therapy; drug withdrawal; female; follow up; gastrointestinal toxicity; gender; gene mutation; human; human tissue; incidence; liver toxicity; major clinical study; male; middle aged; multicenter study; observational study; overall survival; prophylaxis; prospective study; QT prolongation; remission; risk assessment; risk factor; side effect;