Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study

Abstract

Background: Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies. Objective: To evaluate the cutoff serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects. Patients and Methods: A total of 74 patients treated with induction chemotherapy (n = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (n = 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed. Results: The overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25-1.0 µg/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cutoff value of 0.47 µg/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 µg/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses. Conclusion: The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 µg/ml is highly recommended to avoid IFIs after chemotherapy or HSCT.

Deciphering the Relationship Between the Trough Concentration of Posaconazole and Its Efficacy and Safety in Chinese Patients With Hematological Disorders

“…Logistic regression analysis revealed that the PCZ C min value of 0.76 µg/mL was associated with >80% probability of successful therapy ( Wang et al, 2014 ). Similar to a prospective study of PCZ prophylaxis of IFIs in patients with hematological diseases [the success rate was (64/74) 86.5%] ( Li et al, 2020 ), and a randomized clinical trial for prophylaxis against IFIs [the success rate was (85/91) 93.5%] ( Jang et al, 2010 ), the current study found that 83.3% of patients (30/36) successfully responded to PCZ prophylaxis. In agreement with the previous study ( Chau et al, 2014 ), a PCZ C min of 1.0 µg/mL was chosen as the lower limit to treatment of a proven, probable, or possible IFI, and the logistic regression model showed that this C min was associated with a probability of successful response of 80.5% ( Figure 3B ).…”

“…However, real-world data in this field is limited, especially in Asian populations. One Chinese study suggested that the concentration of PCZ affects the probability of response to prophylaxis of fungal infections, but factors, other than PPIs, affecting PCZ concentrations were not investigated so far ( Li et al, 2020 ). One South Korea study suggested that hypoalbuminemia influences PCZ concentrations, but the concentration-to- response relationship was not explored ( Oh et al, 2020 ).…”

Multicenter Registry of Patients Receiving Systemic Mold-Active Triazoles for the Management of Invasive Fungal Infections

“…Almost all patients in the FAS were treated in an inpatient setting at the time of MAT index/enrollment; only two patients in the voriconazole group were treated in an outpatient setting. The median length of the initial hospital stay was 26 days (95% CI [25][26][27], ranging from 23 days (95% CI [21][22][23][24][25][26] in the isavuconazole group to 28 days (95% CI [26][27][28][29][30] in the posaconazole group (Table 6). Overall, around 27% of patients who were hospitalized at index/ enrollment were in the ICU, ranging from 13.6% of patients in the posaconazole group to 36.6% of patients in the isavuconazole group.…”

Posaconazole for secondary antifungal prophylaxis in allogeneic stem cell transplantation recipients: a retrospective study

“…Finally, routine quanti cation of therapeutic drug monitoring for posaconazole is not carried out in clinical practice in this study. In the literature, the plasma concentration of posaconazole was related to the incidence of IFD [23]. This potential posaconazole serum concentration differences would make data analysis more di cult and complex.…”