Introduction
Over the past 20 years or so, invasive fungal diseases (IFDs) have become one of the main causes of death in hematological patients treated with high-intensity chemotherapy and/or a hematopoietic stem cell transplantation (HSCT). IFD detection is challenging due to the low accuracy of early clinical diagnosis and the fact that culture test evidence takes 3 to 5 days to become accessible. As a result, patients who are suspected of having a fungal infection or who have been clinically diagnosed with low neutrophil counts, as well as those who have had transplant surgery, are routinely treated with empirical and preventive medications.
Furthermore, randomised controlled trials have demonstrated that fluconazole prophylaxis can considerably reduce Candida infections and lower the mortality of Candidiasis-infected individuals, proving the efficacy of antifungal prophylaxis. Posaconazole is an extended-spectrum antifungal medication that is more effective than fluconazole or itraconazole in avoiding IFDs and lowering the likelihood of IFD breakthroughs. Posaconazole, a medication from the second generation of triazole medicines, has good toxicity and antifungal effectiveness against new-type resistant pathogen strains.
After voriconazole treatment failed, antifungal posaconazole salvage therapy was shown to be efficacious in 72.2 percent of aggressive Aspergillosis patients in a real-world trial in Germany. Furthermore, prior research found that prophylactic posaconazole medication was beneficial in avoiding IFDs. However others found that certain IFD breakthroughs occurred despite prophylactic posaconazole treatment, which were ascribed to a shift to non-Aspergillus spp. and low posaconazole dosages. The aim of the study was to analyze the efficacy of posaconazole for the prophylaxis and treatment of invasive fungal diseases (IFDs) in patients with hematological malignancies.
Materials and methods
In this retrospective observational multi-center study, 762 patients from 25 Chinese hematological centers were enrolled. Inclusion criteria were patients with hematological malignancy or they had undergone hematopoietic stem cell transplantation and received at least 1 dose of posaconazole. The primary endpoints were the observation of breakthrough rates and the clinical efficacy of posaconazole prophylaxis. The secondary endpoint was the efficacy of posaconazole for the treatment of IFDs.
Of the 762 enrolled patients, 456 (59.8%) were prescribed posaconazole prophylactically while 243 (31.9%) received posaconazole as an IFD treatment (12 proven, 61 probable, 109 possible, and 61 unclassified IFD cases) for ≥7 days (Figure 1)
Results
The overall IFD breakthrough rate (probable cases) for the ≥4 days prophylactic treatment (n = 445) group was 1.6% (95% Cl: 0.6%–3.2%), with breakthrough rates of 2.6% for acute myeloid leukemia/myelodysplastic syndrome patients undergoing chemotherapy and 2.2% for hematopoietic stem cell transplantation patients. For primary antifungal prophylaxis, the breakthrough rate was 1.9% and for secondary antifungal prophylaxis 0%.
The effective remission rates in patients who received posaconazole monotherapy were 58.3% (95% CI: 50.0% to 66.2%, 88/151) and 52.2% (95% CI: 41.5% to 62.7%, 48/92) for patients who received combination therapy of posaconazole with other antifungal drugs. The reasons for switching medications were the same as for prophylactic drugs, that is, mainly cost, side effects, or intolerance.
Effective remission rate after posaconazole as salvage therapy in proven and probable IFD patients after continuous posaconazole therapy for >7 days
Of the 73 proven and probable IFD cases, 34 (46.6%) received posaconazole as salvage therapy. Complete and partial remission was achieved in 1 and 16 of these cases respectively, leading to an effective remission rate of 50% (95% CI: 32.4% to 67.6%; 17/34). Of the 34 patients who received continuously posaconazole as salvage therapy for >7 days, 4 received posaconazole salvage therapy due to Aspergillus-related IFD infections. Complete and partial remission occurred in 1 and 2 cases, respectively, leading to an effective remission rate of 75% (95% CI: 19.4% to 99.4%, 3/4) (Table 1).
Conclusions
This real-world retrospective study confirmed posaconazole as reasonable IFD prophylaxis and treatment medication for hematological patients.
Source: Chen X, Wang J, Wang S, et al. Real-world assessment of the effectiveness of posaconazole for the prophylaxis and treatment of invasive fungal infections in hematological patients: A retrospective observational
study. Medicine (Baltimore). 2021;100(30):e26772. doi:10.1097/MD.0000000000026772
