Primary prophylaxis of invasive fungal infections with posaconazole or itraconazole in patients with acute myeloid leukaemia or high‐risk myelodysplastic syndromes undergoing intensive cytotoxic chemotherapy: A real‐world comparison

Abstract

This is an observational-retrospective study comparing the real-world outcomes associated with posaconazole vs itraconazole as prophylaxis treatments. Two hundred and ninety-three patient admissions attributable to 174 patients were included in the study. Patients were treated with itraconazole (n = 114 admissions; 39%) or posaconazole (n = 179; 61%). Antifungal prophylaxis failure (APF) due to treatment-related adverse events (in 34 out of 293 patient admissions; 11.6%) was more frequent in the posaconazole group (6.1% vs 15.1%; P = .024). There were 9 patient admissions for episodes of APF due to probable/proven breakthrough fungal infection (primary endpoint): 6 and 3 in the itraconazole and posaconazole group respectively (5.3% vs 1.7%; P = .095). All of them were associated with invasive pulmonary aspergillosis (IPA). APF was more frequent with itraconazole (65% vs 30%; P < .001), along with failure due to possible/probable/proven IPA (25% vs 10%; P = .002) and overall failure by any of the 3 different causes of prophylaxis failure (70% vs 38%; P < .001). In agreement with clinical trial data, this real-world evidence supports the use of posaconazole over itraconazole in AML or MDS patients undergoing intensive chemotherapy.

‘Real-life’ analysis of the role of antifungal prophylaxis in preventing invasive aspergillosis in AML patients undergoing consolidation therapy: Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM) 2016 study

“…The rate of our proven/probable breakthrough IA in patients treated with posaconazole was in line with the others' experience. 29 In our experience, AP appears to reduce the risk of IA after the consolidation course and strengthens the efficacy of antifungal therapy. Most of the patients who received AP responded well when the first-line antifungal therapy was instituted, and therefore we can assume that a broad-spectrum AP may decrease the rate of resistant pathogens, enhancing the action of the subsequent antifungal therapeutic regimen.…”

Breakthrough Invasive Mold Infections in the Hematology Patient: Current Concepts and Future Directions

“…Therefore, postmarketing observational cohort studies are critical in developing a broader understanding of the safety and efficacy of any medication. Several cohort studies following the 2 landmark posaconazole prophylaxis clinical trials further highlighted the development of posaconazole-associated bIMIs with variable incidence rates depending on the study (0-10.9%) [6,13,16,[18][19][20][21]. IA caused by A. fumigatus is most often represented among these bIMIs, but IA caused by non-fumigatus Aspergilli and bIMIs caused by non-Aspergillus molds have also been reported including several cases of mucormycosis and fusariosis [6,8,13,16].…”

“…No bIMIs 0% (0/67) [18] Primary prophylaxis in AML/MDS patients with neutropenia during remission-induction chemotherapy; retrospective, single-center observational study IA 1.7% (3/179) [19] Primary prophylaxis in AML/MDS patients with neutropenia during remission-induction chemotherapy; retrospective, single-center observational study Probable bIMI, mucormycosis 2.9% (4/140) [20] Primary prophylaxis in hematology and HSCT patients; retrospective, single-center observational study No bIMIs 0% (0/100) [21] Isavuconazole-associated bIMIs Primary or secondary prophylaxis or primary treatment for IA; retrospective, single-center observational study Mucormycosis most common, IA, fusariosis 6% (6/100) [22] Primary or secondary prophylaxis or treatment of fungal pneumonia; retrospective, single-center observational study and when they occur, high fungal inoculum exposures, suboptimal antifungal pharmacokinetics, and perhaps innate immune gene polymorphisms predominate as drivers [42]. In the latter setting, bIMIs are more frequent, innately resistant non-Aspergillus molds are more common, and host failure due to active hematologic cancer, cumulative immunosuppression (e.g., prolonged corticosteroids) and persistent neutropenia play a role ( Figure 1) [2,3,10,11,43,44].…”

“…Below, we highlight common clinical scenarios and we propose diagnostic and therapeutic algorithms for patients who develop bIMIs, mainly pneumonia, while receiving different mold-active agents, with emphasis on bIMIs developing on mold-active triazoles (especially posaconazole). Because of space constraints, we will not be discussing bIMIs to itraconazole [18,19,[26][27][28][29][30][31] (Table 1) or bIMIs in pediatric patients with hematological cancer.…”

The Effect of Posaconazole Prophylaxes on the Course of Fungal Infection in the High Risk Patients of Hematology: A Single-Center Experience in Turkey

“…In addition, no significant differences were observed in the percentage of developing side effects between the groups (P>0.05) (Table 4). or when unresponsive to standard corticosteroid therapy (40).…”