Utilization of Antifungal Prophylaxis and Treatment for Newly Diagnosed AML Patients Treated with Venetoclax Based Regimens in Routine Clinical Practice - a Prospective Analysis from the Revive Study

Background: Venetoclax (VEN)-based low intensity combinations are approved for the treatment of patients (pts) with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. These combinations can be associated with prolonged cytopenias in particular neutropenia. Invasive fungal infections (IFIs) remain a major cause of morbidity and mortality in pts with AML but their incidence and impact on pts treated with VEN-based low intensity approach are uncertain.

In the current study we assess real-world patterns of IFI's and antifungal treatments among newly-diagnosed (ND) AML patients treated with VEN-based low intensity therapies.

Methods: The REVIVE study is a prospective, real-life, observational study that assesses patterns of pt. selection, efficacy and toxicity. ND pts with AML were enrolled at the time of VEN-based therapy initiation from 12 medical centers in Israel. Demographic, clinical and pt.-related baseline characteristics were documented.

Antifungal medication selection for prophylaxis or therapy use and the incidence of IFIs were documented. The impact of prophylactic antifungal use on the incidence of IFIs and on leukemia related outcomes were assessed.

Results: Between August 12, 2019, and April 15, 2022(data cut) ,189 AML pts were enrolled to receive VEN based therapy.

Overall, the incidence of possible IFIs was relatively low and was observed in 17 patients (9% of patients).

23 pts (12.1%) were reported to have received prophylactic antifungal treatment, whereas 166 pts (87.8%) did not receive. Baseline characteristics of these two groups are shown in Table 1. Of note, pts. receiving antifungal prophylaxis were more likely to be treated as outpatients. A trend towards treatment in a tertiary center and unfavorable ELN risk was observed in pts. receiving antifungal prophylaxis vs. pts not receiving prophylaxis. All other characteristics seemed equally balanced between both groups.

Antifungal prophylaxis included fluconazole (18 pts), voriconazole (6 pts) and posaconzole (1 pt). Of note, 2 patients received two different prophylactic treatments.

The incidence of IFIs was not reduced in pts receiving antifungal prophylaxis. Of the 23 patients who received antifungal prophylaxis, 4 were considered to have an IFI (17.4%) compared with 13 in the non-prophylactic group (7.8%). Antifungal treatment in pts with an IFI included fluconazole (10pts) voriconazole (5 pts) posaconazole (1 pt) amphotericin B (1 pt) and anidulafungin (1pt). Of note, 3 patients received two different antifungal treatments.

No difference in 30-day mortality was observed between the two groups:1 pt in the prophylaxis group died compared with 8 pts in the no-prophylaxis group (4.3% vs 4.8% respectively, p=0.92). Prophylactic antifungal treatment did not affect the rate of adverse events (AEs) leading to treatment discontinuation: 4 pts in the prophylaxis group and 31 pts in the no prophylaxis group discontinued VEN based treatment due to adverse events (17.4% vs 18.7%, p=0.88).

The efficacy of VEN based treatment for AML was similar between pts who received or did not receive antifungal prophylaxis. Composite complete remission (CRc) rates were 60.9% in the antifungal prophylaxis group vs 54.2% in pts with no antifungal prophylaxis (p=0.54). A Kaplan-Meier analysis for overall survival (OS) showed no difference between the prophylaxis and no prophylaxis groups (p=0.505). 1year OS rates were: 50.6% (CI 28-73.3) and 39.4% (CI 30.5-48.3) for prophylaxis and no prophylaxis groups respectively. Median follow up in the prophylaxis group was 237 days (CI 56-878) compared with 173 days (CI 19-850) in the no-prophylaxis group.

Conclusion: In this prospective 'real world' observational study, a low rate of IFIs were noted despite low utilization rates of antifungal prophylaxis, mostly with non-mold active azoles. Moreover, administration of antifungal prophylaxis was not associated with a reduced incidence of IFIs.

Reassuringly, use of antifungal azoles as prophylactic treatment, which requires VEN dose adjustments, did not affect CRc and OS rates. Similarly, azole based prophylaxis did not affect for the rate of treatment discontinuation due to AEs or early mortality.

This study does not support the routine use of antifungal prophylaxis and suggests that such treatment is safe if deemed necessary. Additional insights on antifungal treatment patterns and strategies are pending.

Stemer:Abbvie: Consultancy, Honoraria. Wolach:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jansen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Neopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Levi:Abbvie: Consultancy, Honoraria. Nachmias:AbbVie, BMS: Membership on an entity's Board of Directors or advisory committees, Other: lectures. Tavor:Abbvie: Consultancy. Canaani:AbbVie: Consultancy; Astellas: Consultancy; Medison: Consultancy. Ofran:BMS: Consultancy, Honoraria; Novartis: Consultancy; Janssen: Honoraria; Astellas: Honoraria; Medison: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Zuckerman:Orgenesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BioSight Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cellect Biotechnology: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Tadmor:Janssen: Research Funding; AbbVie, Roche, Novartis, Sanofi, Takeda, Janssen, Pfizer: Consultancy, Honoraria, Speakers Bureau. Cohen:AbbVie: Current Employment. Berelovich:AbbVie: Current Employment. Ofek:Abbvie: Current Employment. Rivlin:AbbVie: Current Employment. Frankel:AbbVie: Current Employment. Grunspan:AbbVie: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Moshe:Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: lectures; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: lectures; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: lectures.