Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Abstract

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug–drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.

The Cologne ECMM Excellence Center: A Two-Year Analysis of External Consultation Service for Invasive Fungal Infections

“…Moreover, while the title of ECMM Excellence Center does not carry an official designation, its acknowledgment can be viewed as an informal nomination, leading to an uptick in consultations from other clinics, both domestically and internationally. Furthermore, the Center's presence and active involvement in national events, initiatives and meetings within Germany may also contribute to the higher number of consultations from this country [ 29 – 31 ]. Closer contact with physicians during these events encourages healthcare professionals to reach out for expert advice and support.…”

Invasive fungal infections in patients with multiple myeloma: a possible growing problem in hematology and infectious diseases

“…due to QTc prolongation); and micafungin can be considered if azole use is not suitable (contraindicated) or there are concerns about drug absorption. 73 , 74 Finally, patients treated with autologous hematopoietic stem cell transplantation, in whom short-term severe neutropenia is expected, can receive prophylactic fluconazole until hematological recovery, especially if mucositis develops.…”

High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies

“…In 2007, a RCT with posaconazole in patients with AML undergoing induction chemotherapy resulted in 2% proven/probable IFDs, compared to 8% with fluconazole or itraconazole, translating to an OS benefit and leading to FDA approval for IFD prevention [ 34 ]. This and other subsequent studies [ 35 , 36 , 37 , 38 , 39 ] placed a large emphasis on the role of MAP in this setting and established posaconazole as the preferred agent for primary AFP undern international guidelines [ 7 , 8 , 9 , 10 , 40 ]. Yeasts, and especially Candida spp., have historically been the most frequent cause of IFDs [ 41 ].…”

“…The most frequently identified fungal pathogens are Aspergillus spp. and Candida spp., which significantly contribute to mortality in these patients [ 2 , 3 , 4 , 5 , 6 ]; therefore, mold-active antifungal prophylaxis (MAP) has been established as a standard of care [ 7 , 8 , 9 , 10 , 11 , 12 ]. However, breakthrough IFDs (b-IFDs) in patients receiving antifungal prophylaxis (AFP), including MAP, is an issue for clinicians, alongside with the rising resistance to antifungals and the continuous change in IFD epidemiology, due to both the increased use of mold-active drugs and the improved survival of HM patients.…”