Noxafil (posaconazole) / Merck (MSD), Ligand - LARVOL DELTA

PHASE 1/2 STUDY OF THE ALL-ORAL COMBINATION OF REVUMENIB (SNDX-5613) WITH DECITABINE/CEDAZURIDINE (ASTX727) AND VENETOCLAX (SAVE) IN RELAPSED/REFRACTORY AML (EHA 2026) - P1/2 | "ASTX727 (35/100 mg) was given PO on days 1–5, venetoclax 400 mg PO on days 1–14, and revumenib 113 mg (DL0) or 163 mg (DL1) PO Q12h on days 1–28 with posaconazole or voriconazole prophylaxis. Summary/Conclusion The all-oral combination of revumenib , venetoclax, and decitabine y ields high remission rates in R/R AML with KMT2Ar , NPM1mt , or NUP98r , with durable responses in patients achieving deep remission. Fig.1: Duration of response by genotype"

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Respiratory Diseases • Thrombocytopenia • BCL2 • KMT2A • NUP98

Risk stratification of ibrutinib toxicity co-administered with triazole antifungals: insights from real-world pharmacovigilance and clinical evidence. (PubMed, Front Med (Lausanne)) - "Voriconazole-containing reports showed a signal for cerebral aspergillosis (ROR = 474.61, n = 3), posaconazole-containing reports showed cardiac events including pericardial effusion (ROR = 24.95, n = 4), and isavuconazole-containing reports showed a signal for febrile neutropenia (ROR = 29.7, n = 4). The identified pharmacovigilance signals are clinically interpretable in light of known CYP3A-mediated pharmacokinetic interactions, but they should be considered hypothesis-generating rather than causal. These findings support clinical awareness, individualized medication review, and further validation in studies with defined denominators and appropriate control of confounding."

Adverse events • Journal • Real-world evidence • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Neutropenia • Pulmonary Disease • Respiratory Diseases

High Response and Prolonged Treatment-Free Remission after a Short-Course of Modified Intensive Chemotherapy and Venetoclax in Elderly AML: An Updated Analysis of the Caveat Trial (ASH 2022) - "Background Venetoclax (VEN) plus azacitidine has an established role in the management of older patients (pts) with AML (DiNardo, NEJM 2020)...We now present an updated analysis of this trial (with >3 years median follow-up), reporting on the optimal dose of VEN with chemotherapy, with and without posaconazole (POSA), the deliverability of consolidation therapy, characteristics of treatment failure and observation of substantial treatment-free remission in subsets of pts using this time-limited, short-course regimen...For induction, VEN was administered over 14 days, commencing with a 7-day pre-chemo dose ramp-up, followed by a 7-day overlap with 5+2 chemotherapy (cytarabine 100mg/m2/d IVI d1-5 and idarubicin 12mg/m2 IV d2-3)...Induction with VEN-POSA (n=18) was also well tolerated (30-day mortality 0%) with 3 DLTs observed: 2 hematologic (1 in each cohort) and 1 due to pulmonary infiltrates occurring on d2 induction (suspected to be allopurinol..."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • Immunology • FLT3 • IDH2 • KIT • NPM1

Final Analysis of the Phase 1b Chemotherapy And Venetoclax in Elderly Acute Myeloid Leukaemia Trial (CAVEAT). (PubMed, Blood Adv) - P1/2 | "Venetoclax plus azacitidine represents a key advance for older, unfit patients with acute myeloid leukemia (AML)...The CAVEAT induction combined cytarabine and idarubicin with 5 dose levels of venetoclax (50-600 mg) for up to 14 days. Two additional cohorts explored adjusted-dose venetoclax (50 mg, 100 mg) with posaconazole...CAVEAT represents an effective time-limited treatment option for fit older patients with AML. (https://www.anzctr.org.au; ACTRN12616000445471)."

Journal • P1 data • Acute Myelogenous Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Early Results of the Phase I/II Study Investigating the All-Oral Combination of the Menin Inhibitor Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE) (ASH 2023) - P1/2 | "ASTX727 (decitabine/ cedazuridine) was administered at 35 mg/100 mg PO daily days 1-5, venetoclax at 400 mg (target dose) PO daily days 1-14, and revumenib 113 mg PO Q12h (dose level [DL] 0) or 163 mg PO Q12h (DL 1, used in phase II monotherapy), days 1-28 with either posaconazole or voriconazole (strong CYP3A4 inhibitors, for antifungal prophylaxis). Early results indicate acceptable safety and high efficacy of this combination in R/R myeloid leukemias with either KMT2Ar or NPM1mt or NUP98r. This study is ongoing with plans to establish the recommended phase 2 dose and optimize delivery of this combination."

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Musculoskeletal Pain • Nephrology • Neutropenia • Oncology • Pain • Renal Disease • Thrombocytopenia • Transplantation • KMT2A • NPM1 • NUP98

Hypomethylating agents with venetoclax for newly diagnosed acute myeloid leukemia in patients 65 and older in The Netherlands - A nationwide study of drug usage and treatment outcomes. (PubMed, Eur J Cancer) - "Our findings showcase how encouraging survival outcomes can be achieved in the real world while simultaneously realizing considerable VEN savings through cycle individualization and strategic usage of drug-drug interactions."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

BGB-11417-103: A Study of BGB-11417 in Participants With Myeloid Malignancies (clinicaltrials.gov) - P1/2 | N=260 | Recruiting | Sponsor: BeOne Medicines | Trial completion date: Feb 2028 ➔ Aug 2028 | Trial primary completion date: Feb 2028 ➔ Aug 2028

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Phase I/II Study of the All-Oral Combination of Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax (SAVE) in R/R AML (ASH 2024) - P1/2 | "ASTX727 (decitabine/ cedazuridine) was administered at 35 mg/100 mg PO daily days 1-5, venetoclax at 400 mg (target dose) PO daily days 1-14, and revumenib 113 mg PO Q12h (dose level [DL] 0) or 163 mg PO Q12h (DL 1, used in phase II monotherapy), days 1-28 with either posaconazole or voriconazole (strong CYP3A4 inhibitors). Conclusions : The all-oral combination SAVE results in high rates of remission in pts with R/R AML with KMT2Ar, NPM1mt or NUP98r. In addition to the R/R cohort, a frontline cohort is now enrolling pts."

IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Metabolic Disorders • Nephrology • Neutropenia • Oncology • Renal Disease • Respiratory Diseases • Thrombocytopenia • KMT2A • NPM1 • NUP98

Phase II Trial of Venetoclax (Ven) in Combination with Azacitidine (AZA) As Maintenance Therapy for High-Risk Acute Leukemia Following Allogeneic Stem Cell Transplantation (SCT) (ASH 2022) - "The majority (63%) received a myeloablative intensity conditioning regimen using intravenous busulfan...After the protocol amendment for VEN to be given as 50 mg on days 1-7 on posaconazole, the requirement for dose changes decreased though still some patients required lower doses of VEN (as 30 mg on days 1-5) on subsequent cycles... Post-SCT maintenance therapy with VEN/AZA was safe and tolerable with favorable results in patients with high-risk AML and ALL. The majority of reported AEs was related to myelosuppression which is a known complication of VEN. Many patients required dose modification of VEN and treatment delays between cycles, highlighting the importance of monitoring these patients very closely."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Transplantation

A Phase II Randomized Trial Comparing Low-Dose Cytarabine and Venetoclax +/- Midostaurin in Non-Adverse Cytogenetic Risk Acute Myeloid Leukemia: The ALLG AMLM25 Intervene Trial (ASH 2024) - "Background For fit patients (pts), combining kinase inhibitors (midostaurin, quizartinib) with intensive chemotherapy is standard of care for FLT3mutated AML...Clonal evolution of kinase-activating mutations, including FLT3-ITD is an important mechanism of treatment failure in pts with non-adverse (NON-ADV) cytogenetic risk AML receiving frontline therapy with azacitidine and venetoclax (AZA-VEN) (DiNardo and Tiong et al, Blood 2020). Incorporating kinase inhibitors (e.g. gilteritinib) into less-intensive VEN-based regimens in unfit, older pts has been challenging, with cumulative myelosuppression a dominant issue (Short et al, JCO 2024)...Posaconazole antifungal prophylaxis was permitted with dose adjustment of VEN to 50 mg daily and MIDO to 50 mg daily due to increased risk of cardiac toxicities in older populations...FLT3­-ITD MRD clearance was observed in 9/15 (60%) in the LVM arm and 1/4 (25%) in the LV arm. Conclusion In unfit, older pts ≥60 years with newly..."

Clinical • P2 data • Acute Myelogenous Leukemia • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Neutropenia • FLT3

Gimema AML1718 Part 1: Planned Interim Analysis of a Safety Run-in and Phase 2 Open-Label Study of Venetoclax, Fludarabine, Idarubicin and Cytarabine (V-FLAI) in the Induction Therapy of Non Low-Risk Acute Myeloid Leukemia (ASH 2022) - P2 | "VEN dose was under situations of concomitant posaconazole administration, discontinued until recovery for patients in remission at day 21 and during consolidation courses; post HSCT maintenance were not allowed. V-FLAI administration was associated with a high and promising CR rate and prolonged OS duration in an intermediate- and high-risk population, without any safety signals. Preliminary MRD analysis revealed deep responses in most of the patients that translated to favorable 1-year survival. The confirmatory arm at the lower effective dosage (VEN 400 mg in combination with FLAI) with centralized MRD assessment is ongoing."

Clinical • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Transplantation • FLT3 • IDH1 • IDH2

Opportunistic Quambalaria fungal endophthalmitis in fumarate-treated multiple sclerosis complicated by multifocal postinfectious cerebral vasculopathy. (PubMed, Retin Cases Brief Rep) - "Quambalaria is an exceptionally rare ocular pathogen that can cause aggressive endophthalmitis. . Vitrectomy and intensive intravitreal voriconazole arrested an infection that had progressed despite treatment; the globe was preserved, although final visual acuity was light perception."

Journal • CNS Disorders • Dermatology • Infectious Disease • Inflammation • Multiple Sclerosis • Ocular Infections • Ocular Inflammation • Ophthalmology • Uveitis

Posaconazole Prophylaxis for the Prevention of Invasive Fungal Infections in Patients With Hematologic Malignancies: A Systematic Review and Meta-Analysis. (PubMed, Eur J Haematol) - "Posaconazole prophylaxis is associated with an approximately halved incidence of ppIFI and a 53% reduction in IFI-related mortality, with greater protection from the DR tablet than from the oral suspension. These findings support posaconazole, particularly the DR tablet formulation, as the preferred agent for primary IFI prophylaxis in high-risk hematological patients, although the limited volume of high-quality randomized evidence warrants cautious interpretation."

Clinical • Journal • Retrospective data • Review • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Oncology • Transplantation

In vitro activity profiles and temporal trends in reduced susceptibility to azoles in Coccidioides in the United States. (PubMed, Antimicrob Agents Chemother) - "Isavuconazole MIC parameters were available during the second period and similar to those of voriconazole. Fluctuations in GM MICs and the percentage of isolates with elevated MICs were observed with fluconazole, itraconazole, and posaconazole, with elevated values observed between 2011 and 2019. Continued surveillance is needed, and outcome data are required to determine if the consistently reduced susceptibility observed with fluconazole or in those infected with strains that have higher MICs results in poorer outcomes in patients with coccidioidomycosis."

Journal • Preclinical • Dermatology • Respiratory Diseases

Rapid Antifungal Susceptibility Classification of Aspergillus Species Using AI-Assisted Analysis of Routine MALDI-TOF MS Spectra: A Proof-of-Concept Study. (PubMed, Ann Lab Med) - "Their performance in predicting susceptibility to four antifungal agents (voriconazole, posaconazole, itraconazole, and amphotericin B) was evaluated using a validation set comprising A. flavus (N=24), A. fumigatus (N=24), and A. lentulus (N=22), based on categorical agreement (CA), very major error (VME), major error (ME), sensitivity, and specificity. However, its clinical performance across species-antifungal agent combinations was limited. Further optimization, evaluation with larger multicenter datasets, and external validation are required before considering clinical adoption."

Journal

POSITRON: A Study of Itraconazole and Posaconazole for Chronic Pulmonary Aspergillosis (clinicaltrials.gov) - P3 | N=220 | Not yet recruiting | Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

New P3 trial • Pulmonary Disease • Respiratory Diseases

Diversity, antifungal susceptibility, and biofilm formation of fish-associated yeasts from freshwater and marine fish. (PubMed, Vet Res Commun) - "Based on CLSI interpretive criteria, 62.5% of Candida isolates were resistant to fluconazole, whereas 9.4% and 28.1% were categorized as susceptible-dose dependent and susceptible, respectively. Among the antifungal agents evaluated, posaconazole exhibited the broadest inhibitory activity, itraconazole the lowest, while amphotericin B showed consistent activity across all isolates...Strong biofilm-producing phenotypes were most frequently associated with C. zeylanoides and C. albicans, whereas all C. tropicalis isolates lacked detectable biofilm-forming capacity. These findings highlight the presence of diverse yeast communities in fish, including isolates with reduced antifungal susceptibility and biofilm-forming capacity, underscoring the need for continued surveillance within food safety and public health contexts."

Journal

Eutectic Itraconazole and Posaconazole System and the Advantages of Its Use in the Amorphous Form. (PubMed, Mol Pharm) - "These results demonstrate, for the first time, that coamorphization at the eutectic composition might suppress LC ordering. The findings highlight the critical role of composition in governing both molecular organization and stability in amorphous pharmaceuticals."

Journal

Dematiaceous fungal keratitis: prevalence, spectrum, clinical features, outcome, and antifungal susceptibility from a tertiary care centre in North India. (PubMed, Med Mycol) - "Antifungal susceptibility testing (AFST) was performed as per the CLSI (Clinical Laboratory and Standards Institute) broth microdilution method (M38-A2) for a panel of 9 drugs including voriconazole, itraconazole, posaconazole, luliconazole, miconazole, ketoconazole, amphotericin-B, natamycin and terbinafine. as the predominant causative agent. In vitro susceptibility of voriconazole demonstrated better performance against DFK isolates."

Journal • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology

My Hospital Journey With Histoplasmosis During Pregnancy. (PubMed, Open Forum Infect Dis) - "In the hospital, she improved with amphotericin B but did not tolerate itraconazole...We decided on amphotericin therapy via OPAT and switched to posaconazole after delivery...I asked my patient if she wanted to contribute, and she wrote the following heartfelt essay. On paper, she and her baby did well, but that does not capture her harrowing journey and difficult decisions like her own words do."

Journal

Molecular characterization and antifungal susceptibility of Aspergillus spp. isolated from critically ill COVID-19 patients: implications for suspected COVID-19-associated pulmonary aspergillosis (CAPA) in a Brazilian tertiary referral hospital. (PubMed, Med Mycol) - "Susceptibility to amphotericin B (AMB), itraconazole (ITZ), voriconazole (VCZ), and posaconazole (PCZ) was determined according to CLSI M38-A2, and cyp51A and its promoter were analyzed in A. fumigatus. Silent cyp51A mutations occurred in three A. fumigatus isolates, while several section Flavi isolates displayed multiazole NWT. These findings highlight diagnostic limitations and emerging azole resistance, supporting susceptibility testing and surveillance."

Journal • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Clinical characteristics, susceptibility profiles, and outcomes of infection with Alternaria species: a 14-year retrospective study. (PubMed, Med Mycol) - "Posaconazole and itraconazole demonstrated low MICs (MIC₅₀/MIC₉₀: 0.06/0.5 and 0.25/0.5 µg/mL, respectively). Voriconazole and isavuconazole showed higher MIC₅₀/MIC₉₀ (1/2 and 2/4 µg/mL)...Interpretive criteria for Alternaria spp. are needed to guide empiric and definitive therapy."

Journal • Retrospective data • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Oncology • Solid Organ Transplantation • Transplantation

The Iranian National Guideline for Invasive Fungal Infections (IFI) in Hematology-Oncology: An Expert Consensus Report. (PubMed, Int J Hematol Oncol Stem Cell Res) - "The resulting consensus established a localized risk-stratification model identifying acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and active graft-versus-host disease (GVHD) patients as high-risk, recommending posaconazole as the primary standard...The existence of this national guideline creates a major advantage in that treatment approaches are unified and standardized across the country. By eliminating discretionary decisions, this document helps to better manage medication use and ultimately improve patient outcomes, regardless of the city in which they are treated or the facilities they are treated at."

Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

Diagnostic and management challenges in dual-pathogen culture-negative endocarditis: a case report of Brucella Canis native valve infective endocarditis and subsequent saccharomyces cerevisiae prosthetic valve infective endocarditis. (PubMed, Diagn Microbiol Infect Dis) - "This case highlights suspecting rough Brucella in culture-negative infective endocarditis, evaluating unexpected molecular fungal detections alongside histology, and tailoring regimens around severe antimicrobial toxicities."

Journal • Cardiovascular • Gastrointestinal Disorder • Infectious Disease

Antifungal consumption in hematology, intensive care units and at hospital level in French hospitals in 2024. (PubMed, J Glob Antimicrob Resist) - "Consumption patterns were consistent with current recommendations. Variations between wards may reflect differences in patient populations and prophylactic or therapeutic prescribing practices. Continued national surveillance, combined with prescribing practice evaluations and studies of local fungal ecology, will contribute to optimizing antifungal prescribing."

Journal • Critical care • Hematological Disorders • Infectious Disease