Posaconazole Prophylaxis for the Prevention of Invasive Fungal Infections in Patients With Hematologic Malignancies:...

Invasive fungal infections (IFIs) pose a life-threatening risk to patients with hematologic malignancies undergoing intensive chemotherapy. Although posaconazole is widely used as a standard prophylactic agent, a comprehensive quantification of its efficacy, particularly regarding formulation-specific benefits and attributable mortality, is needed to guide modern clinical practice.

We aimed to evaluate the clinical efficacy and safety of posaconazole prophylaxis in patients with hematologic malignancies. The review was conducted according to the Methodological Expectations of Cochrane Intervention Reviews (MECIR) standards and reported in accordance with PRISMA 2020. PubMed, SCOPUS, and Embase were searched from inception to July 25, 2026. We included randomized controlled trials, controlled clinical trials, and prospective or retrospective cohort studies enrolling adults (aged ≥ 16 years) with hematologic malignancies or undergoing hematopoietic stem cell transplantation that compared posaconazole prophylaxis with an active comparator or no prophylaxis and reported breakthrough IFI rates. The primary outcome was the incidence of proven or probable IFI (ppIFI). Secondary outcomes were any IFI (proven/probable/possible), breakthrough IFI (btIFI), IFI-attributable mortality, and all-cause mortality.

A total of 83 studies (36 in the meta-analysis; 47 in the narrative synthesis) were included. Posaconazole was associated with a 52% reduction in the incidence of ppIFI (RR 0.48; 95% CI: 0.38-0.61) with low heterogeneity (I² = 8.3%). The benefit was consistent across comparator types (active prophylaxis or no prophylaxis) and was not significantly modified by the mould-active spectrum of the comparator agent (p = 0.058); a nominally significant difference by underlying hematologic malignancy (p = 0.049) was driven by sparse, largely single-study strata and should be interpreted cautiously. The delayed-release (DR) tablet formulation was associated with a further 63% reduction in ppIFI risk compared with the oral suspension (RR 0.37; 95% CI: 0.17-0.82). Posaconazole prophylaxis was also associated with a 53% reduction in IFI-related mortality (RR 0.47; 95% CI: 0.31-0.70). All-cause mortality showed a nonsignificant trend toward reduction (RR 0.89; 95% CI: 0.70-1.13). Narrative synthesis highlighted that therapeutic drug monitoring is essential, with troughs < 0.7 μg/mL significantly increasing breakthrough risk.

Posaconazole prophylaxis is associated with an approximately halved incidence of ppIFI and a 53% reduction in IFI-related mortality, with greater protection from the DR tablet than from the oral suspension. These findings support posaconazole, particularly the DR tablet formulation, as the preferred agent for primary IFI prophylaxis in high-risk hematological patients, although the limited volume of high-quality randomized evidence warrants cautious interpretation.

PROSPERO CRD42024584703.