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 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 Incidence Density of Invasive Fungal Infections during Primary Antifungal Prophylaxis in Newly Diagnosed Acute Myeloid Leukemia Patients in a Tertiary Cancer Center, 2009 to 2011

2013 ◽  
Vol 58 (2) ◽  
pp. 865-873 ◽  
Author(s):  
Marisa Z. R. Gomes ◽  
Victor E. Mulanovich ◽  
Y. Jiang ◽  
Russell E. Lewis ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Cancer Center ◽  
Remission Induction ◽  
Content Type ◽  
First Remission ◽  
Tertiary Cancer Center ◽  
Acute Myeloid

ABSTRACTAlthough primary antifungal prophylaxis (PAP) is routinely administered in patients with acute myeloid leukemia (AML) during remission-induction and consolidation chemotherapy, the impact of PAP on the incidence of invasive fungal infections (IFIs) is not well described. We retrospectively analyzed the incidence of IFIs in 152 patients with AML who had been admitted to a tertiary cancer center between August 2009 and March 2011 and received PAP within 120 days after first remission-induction chemotherapy. We excluded patients who had undergone stem cell transplantation. Patients received a PAP drug with anti-Aspergillusactivity during 72% (7,660/10,572) of prophylaxis-days. The incidence of documented IFIs (definite or probable according to revised European Organization for Research and Treatment of Cancer [EORTC] criteria) was 2.0/1,000 prophylaxis-days (95% confidence interval [CI], 1.23 to 3.04). IFIs due to molds were more common than IFIs due to yeasts (1.5/1,000 prophylaxis-days versus 0.4/1,000 prophylaxis-days;P= 0.01). Echinocandin-based PAP (8.6 and 7.1/1,000 prophylaxis-days, respectively) was associated with higher rates of documented IFIs than anti-Aspergillusazoles (voriconazole or posaconazole) (2.4 and 1.1/1,000 prophylaxis-days, respectively) at both 42 days (P= 0.03) and 120 days (P< 0.0001) after first remission-induction chemotherapy. The incidence of overall (documented and presumed) IFIs (P< 0.001), documented IFIs (P< 0.01), and empirical antifungal therapies (P< 0.0001) was higher during the first 42 days than after day 42. Despite the broad use of PAP with anti-Aspergillusactivity, IFIs, especially molds, remain a significant cause of morbidity and mortality in AML patients, predominantly during the remission-induction phase. Patients receiving echinocandin-based PAP experienced higher rates of IFIs than did those receiving anti-Aspergillusazoles.

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 ( &gt;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 &gt; 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 Incidence and Risk Factors for Breakthrough Invasive Mold Infections in Acute Myeloid Leukemia Patients Receiving Remission Induction Chemotherapy

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Heena P Patel ◽  
Anthony J Perissinotti ◽  
Twisha S Patel ◽  
Dale L Bixby ◽  
Vincent D Marshall ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Multivariable Analysis ◽  
Antifungal Prophylaxis ◽  
Remission Induction ◽  
Invasive Mold Infections ◽  
Acute Myeloid

Abstract Background Despite fungal prophylaxis, invasive mold infections (IMIs) are a significant cause of morbidity and mortality in patients with acute myeloid leukemia (AML) receiving remission induction chemotherapy. The choice of antifungal prophylaxis agent remains controversial, especially in the era of novel targeted therapies. We conducted a retrospective case–control study to determine the incidence of fungal infections and to identify risk factors associated with IMI. Methods Adult patients with AML receiving anti-Aspergillus prophylaxis were included to determine the incidence of IMI per 1000 prophylaxis-days. Patients without and with IMI were matched 2:1 based on the day of IMI diagnosis, and multivariable models using logistic regression were constructed to identify risk factors for IMI. Results Of the 162 included patients, 28 patients had a possible (n = 22), probable, or proven (n = 6) diagnosis of IMI. The incidence of proven or probable IMI per 1000 prophylaxis-days was not statistically different between anti-Aspergillus azoles and micafungin (1.6 vs 5.4, P = .11). The duration of prophylaxis with each agent did not predict IMI occurrence on regression analysis. Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.004–1.081; P = .03) and relapsed/refractory AML diagnosis (OR, 4.44; 95% CI, 1.56–12.64; P = .003) were associated with IMI on multivariable analysis. Conclusions In cases that preclude use of anti-Aspergillus azoles for prophylaxis, micafungin 100 mg once daily may be considered; however, in older patients and those with relapsed/refractory disease, diligent monitoring for IMI is required, irrespective of the agent used for antifungal prophylaxis.

scholarly journals Survival Benefits from Antifungal Prophylaxis and a Dedicated Inpatient Malignant Hematology Service during Induction Chemotherapy for Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3436-3436
Author(s):  
Andrew Hsu ◽  
Robert Matera ◽  
John L. Reagan ◽  
Dimitrios Farmakiotis
Keyword(s):  
Acute Myeloid Leukemia ◽  
Hospital Mortality ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Post Discharge ◽  
Post Induction ◽  
Acute Myeloid

Introduction: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myeloid leukemia (AML). During induction chemotherapy for AML patients, antifungal prophylaxis (AP) has been associated with a decreased incidence of IFIs and increased survival. However, some centers do not use AP, as it is unclear whether it improves outcomes in settings where the incidence of IFIs is low (&lt;8% of mold infections), as at our center. We retrospectively assessed the differences in clinical outcomes and resource utilization in patients undergoing induction chemotherapy for AML before and after implementation of an AP policy and a dedicated inpatient malignant hematology service at our institution. Methods: AML patients ≥18 years of age who underwent induction chemotherapy between 1/1/07 and 4/1/19 were identified by pharmacy records. Data was verified and extracted by two members of the research team. Primary endpoints were in-hospital mortality during induction chemotherapy and rates of fungal infections within 90-days after induction. Secondary endpoints were 30-day post induction and 90-day post-discharge survival, rates of proven/probable IFI by application of the Mycoses Study Group definitions, diagnostic resource utilization and tolerability. Categorical variables were compared with x2 or Fisher's exact tests and continuous variables with independent samples t-test or the non-parametric Mann-Whitney test as appropriate. Post-induction survival was also analyzed with Kaplan-Meier (KM) curves. Results: 108 adult AML patients were retrospectively reviewed. Fifty-six received AP during induction and 52 did not, without significant differences in demographic or leukemia-specific factors. AP was associated with numerically less fungal infections (9/56 (16%) vs. 14/52 (27%), P=0.169) and proven/probable IFIs (3/52 (6%) vs. 0/56, P=0.1). AP was also associated with lower in-hospital (11/52 (21%) vs. 4/56 (7%), P=0.035) mortality. Clinicians obtained more electrocardiograms (median 4 vs. 1.5, P&lt;0.001) in the AP group; otherwise, there were no significant differences in the number of imaging studies, bronchoscopies, blood cultures, β-D-glucan and Aspergillus galactomannan tests, or adverse events, specifically clinically significant QT prolongation, nephrotoxicity or hepatotoxicity. Antifungals were more likely to be started in the non-prophylaxis group (36/52 (69%)) than changed in the prophylaxis group (23/56 (41%), P=0.003). Implementation of a dedicated inpatient malignant hematology service led to standardization of practices including AP (24/76 (32%) vs. 32/32 (100%), P&lt;0.001) and was associated with significantly lower in-hospital (14/76 (18%) vs. 1/32 (3%), P=0.036) and 90-day post-discharge (16/71 (23%) vs. 1/29 (3%), P=0.021) mortality. Before implementation of this service, AP was associated with numerically lower in-hospital mortality during induction (3/24 (13%) vs. 11/52 (21%), P=0.366), and significantly improved 30-day post-induction survival (Fig. 1, log-rank P=0.042). Conclusions: In a setting where mold infections are rare, AP in patients undergoing induction chemotherapy for AML was associated with improved survival, empiric or targeted antifungal treatment, and a signal for decreased frequency of fungal infections, without substantial increases in utilization of diagnostic resources. This study is limited in its single-center retrospective study design, the overall small number of patients, and is confounded by simultaneous changes in practice, especially with the implementation of a dedicated malignant hematology service. Notably however there was improved 30-day mortality in patients on AP versus those not on AP prior to the implementation of the malignant hematology service. Our findings indicate that outcomes are optimized when adult patients with AML receive their care by a dedicated malignant hematology team, with implications for low-volume institutions and community practices, where AML inductions are not always performed under the care of malignant hematology specialists. Our results suggest that AP and admitting or transferring adult AML patients to a center with a dedicated malignant hematology service, when feasible, may lead to better outcomes. Figure 1 Disclosures Farmakiotis: Astellas: Research Funding; Viracor-Eurofins: Consultancy, Research Funding.

Sign in / Sign up

Export Citation Format

Share Document