Low Rates of Documented Infection in Patients with Acute Myeloid Leukemia (AML) Receiving Venetoclax + Hypomethylating Agents (VEN-HMA)

Introduction

Infection is a major complication in patients with AML receiving intensive induction chemotherapeutic regimens, and antibacterial and antifungal prophylaxis are common practices. However, for patients receiving VEN-HMA regimens, antimicrobial prophylaxis is not the standard of care due to potentially lower infection rates. Furthermore, the use of azoles and quinolones requires dose adjustments for venetoclax because they inhibit its main metabolic pathway. In this study, we evaluated antimicrobial prophylaxis practices and documented infection rates in patients with AML or MDS treated with VEN-HMA.

Methods

This is a multicenter retrospective study conducted in 12 Brazilian centers. We included patients (pts) with AML or MDS who were treated with VEN-HMA either as first-line or salvage therapy. We collected data on antibacterial and antifungal prophylaxis practices, documentation of infection during neutropenia, and outcomes.

Results

A total of 92 patients were analyzed; 66% were male, and the median age was 69 years (range 19-89). Most patients had AML (91%) with high-risk disease (64%), and azacytidine was given to all but 4 patients. VEN-HMA was given as first-line therapy to 60 pts and as salvage therapy to 32 pts (of whom 19 received it as second-line therapy). The first cycle of VEN-HMA was given on an outpatient basis in 34.5% of patients. Quinolone prophylaxis was given to 12 pts (13%) and anti-Aspergillus azole to 6 pts (6.5%). Twenty patients (21.7%) received an echinocandin as antifungal prophylaxis. Febrile neutropenia occurred in 54.7% of patients, with 43.5% classified as fever of unknown origin, 23.9% as clinically documented, 21.7% as microbiologically documented infection, and 10.9% as bacteremia (Gram-negative bacilii in 3 and coagulase-negative staphylococci in 2). Proven or probable invasive fungal disease (IFD) was diagnosed in 7.6% (aspergillosis in 4, and candidiasis, fusariosis, and trichosporonosis in 1 case each). There were no differences in antimicrobial prophylaxis practices or infection documentation between patients receiving VEN-HMA as first-line therapy and those receiving it as salvage therapy. The death rate after cycle 1 was 7.6% and the rate of complete remission (CR) + CR with incomplete hematologic recovery was 51% (58% in first-line therapy). In cycles 2 and 3, febrile neutropenia occurred in 19.7%, and 17.3%, respectively, with 1 case of bacteremia (cycle 3) and no case of IFD.

Conclusions

In the present study, we observed a low rate of bacteremia and IFD despite a low frequency of antibacterial (13%) and anti-mold prophylaxis (6.5% with azoles, 21.7% with echinocandins). The rates of febrile neutropenia and documented infection after the second and third cycles were also very low. These data suggest that antimicrobial prophylaxis should not be routinely given to AML/MDS patients receiving the first cycle of VEN-HMA. Additionally, antimicrobial prophylaxis should be discouraged in subsequent cycles.

Costa Neto:AstraZeneca: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding, Speakers Bureau; Regeneron: Research Funding; AbbVie: Research Funding, Speakers Bureau; Knight Therapeutics: Speakers Bureau; Eli Lilly and Company: Speakers Bureau; Roche: Research Funding; Beigene: Research Funding. Mauad:Roche: Speakers Bureau; Novartis: Speakers Bureau; Pint Pharma: Speakers Bureau. Nucci:Abbott: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Knight: Consultancy, Speakers Bureau; Takeda: Consultancy; Pfizer: Consultancy, Speakers Bureau; F2G: Consultancy; Cidara: Consultancy; Basilea: Consultancy; Teva: Speakers Bureau; MSD: Speakers Bureau; Astellas: Speakers Bureau; Pharmalab: Speakers Bureau; GSK: Speakers Bureau; AstraZeneca: Speakers Bureau.