scholarly journals 986. Incidence of Invasive Fungal Infections in Previously Untreated Patients with Acute Myeloid Leukemia Receiving Venetoclax and Azacitadine

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S584-S584
Author(s):  
Tanit Phupitakphol ◽  
Tanner M Johnson ◽  
Diana Abbott ◽  
Jonathan Gutman ◽  
Daniel Pollyea ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Standard Of Care ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Significant Difference ◽  
The Impact ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) is associated with poor prognosis, particularly in elderly patients with co-morbidities. Low-intensity therapies like azacitidine (aza) were the standard of care and were associated with low response rates and limited survival. Combining venetoclax (ven) with aza demonstrated significant improvements in responses and survival compared to aza alone, and represents the new standard of care for this population. However, as a myelosuppressive regimen, infectious complications, especially invasive fungal infections (IFI), are a potential concern. The incidence of IFI and the role for antifungal prophylaxis have not been well defined for newly-diagnosed AML patients receiving ven/aza. Methods We conducted a retrospective cohort review of AML patients treated with ven/aza at the University of Colorado Hospital from January 2014 to August 2020. Duration of therapy was defined as the time from initiation of treatment through one of the following endpoints (1) patient discontinuation, (2) progression of disease, (3) bone marrow transplantation, or (4) death. Four patients with a history of prior IFI were excluded. We assessed the impact of patient age, sex, duration of neutropenia, antifungal prophylaxis, and AML specific risk factors on the incidence of IFI as defined by the European Mycoses Study Group. Results One hundred forty-four AML patients were included in the study. Ten patients received antifungal prophylaxis and none developed IFI (p=0.21). Twenty-five (17%) patients developed IFI: 2 (8%) had proven IFI, 6 (24%) probable IFI, and 17 (68%) possible IFI. Invasive pulmonary aspergillosis represented all 25 cases of proven, probable, and possible IFI. There was a statistically significant association between prolonged neutropenia ( >60 days) and IFI (p=0.007), whereas age, sex, and SWOG classification were not significantly associated with IFI. Conclusion The incidence of IFI in our AML cohorts treated with ven/aza was 17%, lower than that reported at other institutions. Neutropenia > 60 days was significantly associated with IFI in our AML cohort treated with ven/aza. Although we were not powered to determine whether antifungal prophylaxis impacted IFI, there was no significant difference in IFI for patients who received prophylaxis. Disclosures All Authors: No reported disclosures

scholarly journals Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents

2019 ◽  
Vol 3 (23) ◽  
pp. 4043-4049 ◽  
Author(s):  
Ibrahim Aldoss ◽  
Sanjeet Dadwal ◽  
Jianying Zhang ◽  
Bernard Tegtmeier ◽  
Matthew Mei ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Hypomethylating Agents ◽  
Key Points ◽  
Acute Myeloid

Key Points The incidence of IFIs during VEN-HMA therapy is low, and the used antifungal prophylaxis approach did not influence the risk of IFIs. The risk of IFIs is higher in nonresponders and those who were treated in the r/r AML setting.

scholarly journals 1301. Breakthrough Invasive Fungal Infections based on CYP2C19 Levels in Patients Who were on Voriconazole as Primary Antifungal Prophylaxis in Acute Myeloid Leukemia (AML) undergoing Induction Chemotherapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S665-S665
Author(s):  
Hareesh v Singam ◽  
Yanina Pasikhova ◽  
Rod Quilitz ◽  
John N Greene ◽  
Aliyah Baluch
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Intermediate Metabolizers ◽  
Acute Myeloid

Abstract Background Voriconazole (Vori) is often used for prophylactic anti-fungal therapy in induction chemotherapy for Acute Myeloid Leukemia (AML) patients due to predictable absorption and an extended spectrum antifungal activity. Vori is metabolized predominately by CYP2C19 to metabolites with less antifungal activity. There has been a great interest in understanding CYP2C19 as it significantly affects drug metabolism and pharmacokinetics of numerous drugs including voriconazole. Approximately 39% of patients are genetically predicted to be CYP2C19 ultra-rapid or rapid metabolizers and thus are at an increased risk of breakthrough fungal infection. This study assesses the incidence of breakthrough invasive fungal infections (bIFI) at Moffitt Cancer Center based on CYP2C19 activity. bIFI is defined as new fungal infection while on vori, leading to treatment with liposomal amphotericin B, echinocandin, and/or different triazole. Methods This is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML and received voriconazole as the primary antifungal prophylaxis between July 2017 and June 2019. The patients enrolled were over 18 years old and did not have a history of stem cell transplant or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or received systematic antifungal therapy 30 days prior. CYP2C19 were checked for each of the patients between July 2017 to June 2019 who were undergoing induction chemotherapy for newly diagnosed AML. It was checked within one week of admission. The patients were categorized as rapid metabolizers, intermediate metabolizers, normal metabolizers, and unknown CYP2C19. Results There was an incidence of 20.2% (18/89) bIFI in patients who were on Vori in this study. Of these patients with bIFI infections, 15.7% (3/19) of patients were rapid metabolizers, 14.7% (5/34) were normal metabolizers, 28.5% (4/14) were intermediate metabolizers and 0% (0/3) were poor metabolizers. There were 31% (6/19) breakthrough infections in patients with unknown CYP2C19 characteristics. Conclusion There is no significant statistical difference (p=0.6) among CYP2C19 categories with respect to breakthrough of invasive fungal infections at Moffitt Cancer Center between July 2017 - June 2019. Disclosures Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)

scholarly journals 1735. Epidemiology of Invasive Fungal Infections During Induction Chemotherapy in Adults With Newly Diagnosed Acute Myeloid Leukemia Without Antifungal Prophylaxis: A Retrospective Cohort Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S635-S636
Author(s):  
Eugenia Miranti ◽  
Kyle Enriquez ◽  
Bruno Medeiros ◽  
Aruna Subramanian ◽  
Dora Ho ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Patient Population ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Current Data ◽  
Invasive Fungal Infections ◽  
Pseudallescheria Boydii ◽  
Acute Myeloid

Abstract Background While invasive fungal infections (IFIs) are common in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy, little current data exist on the epidemiology of IFIs in this patient population given widespread use of antifungal prophylaxis. Because our institution does not administer antifungal prophylaxis, we are in a unique position to study the natural history of IFIs in these patients. Methods We evaluated the incidence of IFIs using established definitions in adults with AML undergoing induction chemotherapy at Stanford Health Care from 2012 to 2017. We also analyzed incidence of antifungal treatment, impact of IFI diagnosis on survival, and risk factors for IFI development. Patients were followed for up to 12 weeks after beginning induction chemotherapy. Results Of 488 patients analyzed, 243 were eligible for inclusion. The median age was 57 (interquartile range 45–65). Men composed 134 (55%) of the patients and 157 (65%) where white. Fifty-four (22%) had antecedent myelodysplastic syndrome; most received a “7 + 3” regimen involving cytarabine and an anthracycline. Thirty-one (13%) developed a proven or probable IFI; 104 (43%) developed a proven, probable, or possible IFI. Most IFIs were due to lower respiratory tract disease. Eighteen identified organisms were Candida, including six C. albicans. Eight organisms were mold, including four Aspergillus isolates (all but one A. fumigatus) and one isolate each of Fusarium solani, Rhizomucor, Rhizopus, and Scedosporium apiospermum/Pseudallescheria boydii. One hundred ninety patients (78%) received antifungals during their initial admission and 99 (46%) of patients surviving their initial admission were discharged on antifungals. Only 66.7% of patients with a proven or probable IFI survived through 12 weeks, compared with 92.2% of those without (P = 0.007). Baseline absolute neutrophil count ≤500 cells/μL and longer duration of neutropenia were significantly associated with development of proven or probable IFIs. Conclusion Among patients receiving induction chemotherapy for AML, IFIs due to Candida and mold remain frequent absent antifungal prophylaxis and are associated with worse survival. Our findings support the use of antifungal prophylaxis in this patient population. Disclosures All authors: No reported disclosures.

scholarly journals 742. Breakthrough Invasive Fungal Infections with Isavuconazonium Sulfate versus Voriconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia (AML) who Received Induction Chemotherapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S419-S419
Author(s):  
Hareesh v Singam ◽  
Yanina Pasikhova ◽  
Rod Quilitz ◽  
John N Greene ◽  
Aliyah Baluch
Keyword(s):  
Acute Myeloid Leukemia ◽  
Retrospective Analysis ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Cancer Center ◽  
Solid Organ ◽  
Acute Myeloid

Abstract Background Fungal infections in patients with hematologic malignancies are associated with high mortality. Primary antifungal prophylaxis has been shown to be a more effective strategy than treating a documented infection. This retrospective analysis aims to compare the rates of breakthrough invasive fungal infections in patients with acute myeloid leukemia (AML) who received induction chemotherapy and were prescribed voriconazole (Vori) or isavuconazonium (Isv) for primary antifungal prophylaxis. The European Organization for Research and Treatment of Cancer/ Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to categorize incidence of breakthrough invasive fungal infections bIFI into ‘possible’, ‘probable’ or ‘definite’ groups who required treatment with liposomal amphotericin B, echinocandin, and/or different triazole. Methods This is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML. These patients received either Vori or Isv sulfate as the primary antifungal prophylaxis at Moffitt Cancer Center between July 2017 and June 2019. Patients who were over 18 years old and received at least 10 days of uninterrupted primary antifungal prophylaxis with either Vori or Isv sulfate were included in the study. Patients with a history of stem cell or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or who received systematic antifungal, other than fluconazole, therapy within 30 days to induction chemotherapy were excluded. Results 250 patients were screened for the study and out of which 118 patients met the above criteria. There was a 20.2% (18/89) break through rate of fungal infections in the Vori arm and 17.2% (5/29) in the Isv arm. In the Vori arm there were 15 possible bIFIs, 3 probable bIFIs and 0 definite bIFIs. In the Isv arm there are 2 possible bIFIs, 2 probable bIFIs and 1 definite bIFIs. Conclusion There is no significant statistical difference (Using the Fisher Exact test statistic p=1) between the Isv and Vori in patients who received these agents for primary fungal prophylaxis for induction chemotherapy for AML at Moffitt Cancer Center between July 2017 - June 2019. Disclosures Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)

scholarly journals Infections of Venetoclax-Based Chemotherapy in Acute Myeloid Leukemia: Rationale for Proper Antimicrobial Prophylaxis

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6285
Author(s):  
Raeseok Lee ◽  
Sung-Yeon Cho ◽  
Dong-Gun Lee ◽  
Hyeah Choi ◽  
Silvia Park ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antimicrobial Prophylaxis ◽  
Standard Of Care ◽  
Infectious Complications ◽  
Antifungal Prophylaxis ◽  
High Dose ◽  
Acute Myeloid ◽  
Overall Mortality

Although venetoclax (VEN)-based combination chemotherapy in patients with acute myeloid leukemia (AML) results in prolonged and profound neutropenia, data regarding infectious complications and antimicrobial prophylaxis are lacking. We investigated the infectious complications in 122 adult patients with AML under the same standard of care for prevention. The prophylaxis protocol was fluconazole 400 mg/d without antibacterial agents. The incidence of proven or probable invasive fungal infections (IFIs) was 6.6/100 cycles, and 22 patients (18.0%) were diagnosed (median, second cycle; interquartile range, 1–2). All IFIs were caused by Aspergillus and significantly influenced the overall mortality (odds ratio (OR), 2.737; 95% confidence interval (CI), 1.051–7.128; p = 0.034). In the multivariate analysis, secondary or therapy-related AML was an independent risk factor for IFIs (OR, 3.859; 95% CI, 1.344–11.048, p = 0.012). A total of 39 bloodstream infection (BSIs) episodes occurred in 35 patients (28.7%), with an incidence of 12.7/100 cycles. High-dose steroid administration within 90 days was associated with the occurrence of BSIs (OR, 7.474; 95% CI; 1.661–3.631, p = 0.008), although BSIs themselves did not have an impact on the outcomes. Our findings suggest evidence for the need for mold-active antifungal agents as antifungal prophylaxis, rather than fluconazole, especially in patients with secondary or therapy-related AML.

Incidence of Invasive Fungal Infections in Acute Myeloid Leukemia Without Antifungal Prophylaxis

2020 ◽  
Vol 20 (11) ◽  
pp. e883-e889
Author(s):  
Jessie Signorelli ◽  
Matthew Lei ◽  
Jenna Lam ◽  
Marla Jalbut ◽  
Philip C. Amrein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Acute Myeloid
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