Synribo (omacetaxine mepesuccinate) / Teva, ArchiMed - LARVOL DELTA

Clinical efficacy analysis of seven pediatric patients with Acute myeloid leukemia and the t(16;21)(p11;q22) FUS::ERG fusion gene (PubMed, Zhonghua Yi Xue Yi Chuan Xue Za Zhi) - "The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival."

IO biomarker • Journal • Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation • ANPEP • CD123 • CD33 • CD34 • CD38 • ERG • FUS • IL3RA • ITGAM • KIT • NCAM1

THE EFFECT OF ALLOGENEIC HSCT ON PEDIATRIC NON–DOWN SYNDROME AMKL: RESULTS FROM A MULTICENTER CALD-AMKL-18 TRIAL (EBMT 2026) - P1/2 | "In this study we investigated the effect of allogeneic hematopoietic stem cell transplantation (HSCT) on the outcome of non-DS AMKL CALD-AMKL-18 is a prospective multicenter trial using a low-dose HAG induction backbone (low-dose of homoharringtonine and cytarabine, routine dose of G-CSF) for newly diagnosed pediatric non-DS AMKL at 9 Chinese centers. CR1 HSCT appeared to improve survival for some adverse genotypes. These data support a risk-adapted HSCT strategy built on a low-toxicity HAG backbone, but also highlight the need for "low-dose chemotherapy (LDC) + X" approaches that integrate targeted agents and MRD-guided HSCT to overcome fusion-driven resistance in pediatric non-DS AMKL."

Clinical • Bone Marrow Transplantation • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Pediatrics • CBFA2T3 • CCDC6 • CSF1R • ETV6 • GATA1 • GLIS2 • KDM5A • KMT2A • MLLT10 • MLLT3 • MRTFA • NUP98 • PRKAR1A • RBM15 • RUNX1 • ZEB2

Olverembatinib (HQP1351) Demonstrates Efficacy Vs. Best Available Therapy (BAT) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant Chronic Myeloid Leukemia Chronic-Phase (CML-CP) in a Registrational Randomized Phase 2 Study (ASH 2023) - P2 | "Introduction This was a multicenter, randomized, registrational phase 2 study to assess the efficacy and safety of olverembatinib compared with BAT in pts with CML-CP who were resistant and/or intolerant to 3 TKIs (imatinib [I], dasatinib [D], nilotinib [N]) in China...Pts were randomized 2:1 to investigational olverembatinib (40 mg QOD) or the BAT arm, which could be one of the following per investigator choice: TKIs (I, D, or N), interferon (IFN), hydroxyurea (HU), and homoharringtonine (HHT)...Olverembatinib was observed to be better tolerated and more effective than BAT in treating these pts. Internal study (CT.gov) numbers: HQP1351CC203 (NCT04126681)."

Clinical • P2 data • Anemia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Leukemia • Leukopenia • Myocardial Infarction • Neutropenia • Oncology • Thrombocytopenia • ABL1

Targeting Hippo-YAP/TAZ signaling pathway: an updated review demonstrating the therapeutic potential of key plant derived anticancer compounds. (PubMed, Front Pharmacol) - "The upregulation of YAP/TAZ/TEAD complex has been demonstrated to result in cellular proliferation, transformation, and ultimately, carcinogenesis. This article offers extensive insight into plant derived anticancer compounds mainly apigenin, curcumin, EGCG, resveratrol, homoharringtonine, and ursolic acid of the Hippo pathway, specifically YAP/TAZ, in several cancer therapies. This will enhance the discovery of novel Hippo inhibitors and the optimal therapeutic application of Hippo signaling-related pharmaceuticals in synergistic cancer therapies."

Journal • Review • Oncology

Screening of FDA-approved drugs using a recombinant Cedar virus to improve treatment options for Nipah virus infection. (PubMed, J Gen Virol) - "Using recombinant Cedar virus expressing luciferase (rCedV-Luc) as a CL2 surrogate, we screened a library of 2,703 Food and Drug Administration (FDA)-approved compounds, yielding 5 promising candidates: bortezomib, harringtonine, homoharringtonine, ixazomib citrate and lanatoside C. Compounds demonstrated low half-maximal inhibitory concentration (IC50) values of ≤0.45 µM and high selectivity indexes >6 in mammalian cell lines. Time-of-addition studies suggest that these compounds target a post-entry stage of henipavirus replication. This study demonstrates the utility of rCedV-Luc as a surrogate for the antiviral screening of henipaviruses and identification of promising candidates for further investigation and development as henipavirus antivirals."

FDA event • Journal • Preclinical • Infectious Disease

SRSF2 mutations drive daunorubicin resistance in acute myeloid leukemia via THBS1 stabilization. (PubMed, J Exp Clin Cancer Res) - "SRSF2 mutations promoted DNR resistance through multiple mechanisms, and targeted combination therapy with PDGFB pathway inhibitors may represent a novel strategy to improve therapeutic outcomes in patients with mutations."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • PDGFB • SRSF2 • THBS1

Omacetaxine and venetoclax in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome with mutant RUNX1. (PubMed, Blood Neoplasia) - P1/2 | "Clinical responses were seen exclusively in patients with MDS, which suggests that dose optimization or combination with cytoreductive agents may be necessary for eliciting clinical activity in AML. This trial was registered at www.ClinicalTrials.gov as #NCT04874194."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • BCL2L1 • MCL1 • RUNX1

Cladribine Plus Homoharringtonine and Cytarabine Regimen (CHA) for de Novo Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=65 | Completed | Sponsor: First Affiliated Hospital of Zhejiang University | Recruiting ➔ Completed | N=30 ➔ 65 | Trial primary completion date: Aug 2025 ➔ Apr 2025

Enrollment change • Trial completion • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Venetoclax Combined with Hag Regimen in Newly Diagnosed ETP-ALL: A Prospective, Multicenter, Phase 2 Trial (ASH 2024) - "The V-HAG regimen included venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14; if the blast cells in the bone marrow (BM) were more than 5% on day 14, the patient continued to receive venetoclax 400 mg until day 28), homoharringtonine (1.4 mg/m², maximum 2 mg daily, intravenously from days 1-10), low-dose cytarabine (10 mg/m² subcutaneously every 12 hours on days 1-14), and G-CSF (200 µg/m² daily on days 1-14 if the WBC <10*109/L). Conclusions : Venetoclax Combined with HAG regimen achieved an 100% CRc rate in newly diagnosed ETP-ALL. This therapy is a promising and well-tolerated regimen in newly diagnosed ETP-ALL patients."

Clinical • P2 data • Acute Lymphocytic Leukemia • Anemia • Basal Cell Carcinoma • Bone Marrow Transplantation • Chronic Obstructive Pulmonary Disease • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Melanoma • Neutropenia • Non-melanoma Skin Cancer • Oncology • Respiratory Diseases • Solid Tumor • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Thrombocytopenia • Thyroid Gland Carcinoma • Tuberculosis

Therapeutic Effects of Cephalotaxus harringtonia Leaf Extract on Hepatocellular Carcinoma via Regulation of the Intrinsic Apoptosis Pathway and Cell Cycle. (PubMed, Curr Issues Mol Biol) - "Cephalotaxus harringtonia, traditionally used in East Asian medicine, contains several bioactive constituents, including homoharringtonine (HHT) and quercetin 3-β-D-glucoside (Q3G), which are known for their anticancer properties...Mechanistic analyses revealed that CHLE induced apoptosis through a mitochondria-mediated intrinsic pathway, characterized by increased reactive oxygen species production, mitochondrial membrane depolarization, and BAX upregulation. These findings demonstrate that C. harringtonia leaf extract possesses potent, selective anticancer activity and may serve as a promising natural candidate for the prevention and therapeutic management of liver cancer."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Efficacy and safety of sequential therapy with Venetoclax, Azacitidine, and Homoharringtonine in elderly patients with de novo AML: A prospective, single-arm, multicenter, exploratory clinical trial (ChiCTR) - P=N/A | N=40 | Not yet recruiting | Sponsor: the First Affiliated Hospital, Zhejiang University School of Medicine; The People's Hospital Affiliated to Ningbo University

New trial • Acute Myelogenous Leukemia

NETWORK-BASED PROTEOMIC SIGNATURES REVEAL DIAGNOSTIC BIOMARKERS AND REPURPOSABLE THERAPEUTICS IN PARKINSON'S DISEASE (ADPD 2026) - "Drug perturbation mapping identified SAL-1, fostamatinib, homoharringtonine, and 2-aminopurine as candidates capable of reversing PD-associated proteomic signatures. Our findings demonstrate that proteomics-based models outperform RNA-based and multimodal approaches in classifying PD and tracking disease severity. The identified biomarkers are functionally enriched in extracellular and immune-related processes, offering insight into PD pathophysiology. Network-informed perturbation analysis further nominates candidate therapeutics for experimental validation."

Biomarker • CNS Disorders • Movement Disorders • Parkinson's Disease

Discovery of novel and potent harringtonine derivative P2 via systematic structure-activity Optimization: Semi-Synthesis, anti-leukemia activity, and mechanism study. (PubMed, Eur J Med Chem) - "P2 exhibited a ∼10-fold increase in antiproliferative potency against human leukemic cell lines compared to homoharringtonine (HHT)...Our findings provide valuable insights to guide the future structural optimization of harringtonine derivatives. Furthermore, P2 has been identified as a promising anti-leukemic candidate and warrants further development."

Journal • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • MCL1 • MYC

Transcriptome-Guided Drug Repurposing Identifies Homoharringtonine (HHT) as a Candidate for Radiation-Induced Pulmonary Fibrosis. (PubMed, Pharmaceutics) - "This study highlights the value of computational drug repurposing platforms for accelerating therapeutic discovery. Further preclinical investigations are warranted to evaluate HHT's in vivo efficacy and clinical applicability in RPF."

Journal • Fibrosis • Immunology • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • CCND1 • RHOA

Homoharringtonine suppresses acute myeloid leukemia progression by orchestrating EWSR1 phase separation in an m6A-YTHDF2-dependent mechanism. (PubMed, Imeta) - "In vivo, the anti-leukemic efficacy of HHT was significantly diminished upon EWSR1 knockdown, demonstrating that EWSR1 was required for therapeutic response. Collectively, these findings uncover a phase separation-centric mechanism by which HHT exerts anti-AML activity, establish the EWSR1-YTHDF2-m6A axis as a critical regulator of leukemia progression, and position EWSR1 as both a functional target and a predictive biomarker for optimizing HHT-based therapies."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • EWSR1 • HMOX1 • TNFRSF1B • YTHDF2

Organoid-based drug screening identifies homoharringtonine as a therapeutic agent for anaplastic thyroid cancer via TFEB-mediated lysosomal dysfunction. (PubMed, Cell Oncol (Dordr)) - "Our study demonstrates the utility of cancer organoids in drug discovery and identifies HHT as a promising therapeuticagent for ATC."

Journal • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • TFEB

Olverembatinib (HQP1351) demonstrates efficacy vs. best available therapy (BAT) in patients (pts) with tyrosine kinase inhibitor (TKI)-resistant chronic-Phase chronic myeloid leukemia (CML-CP) in a registrational randomized Phase 2 trial: Up to 4-year follow-up including patients without T315I mutations (ASH 2025) - P2 | "Introduction This was a multicenter, randomized, registrational phase 2 study to assess efficacy and safety ofolverembatinib vs. BAT in pts with CML-CP resistant and/or intolerant to three TKIs (imatinib [I]), dasatinib[D], nilotinib [N]) in China...Pts were randomized 2:1 to olverembatinib (40 mg QOD) or the BAT arm: TKIs (I, D, or N),interferon, hydroxyurea, and/or homoharringtonine by investigator choice...Olverembatinib was more efficacious andbetter tolerated than BAT in treating these pts (including those without T315I mutations). Internal study(CT.gov) numbers: HQP1351CC203 (NCT04126681)."

Clinical • P2 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Neutropenia • Thrombocytopenia • ABL1

Efficacy and safety of azacitidine, venetoclax combined with gha priming regimen in the treatment of adult refractory and relapsed acute myeloid leukemia: A prospective single-arm multicenter study (ASH 2025) - "These patients were treated with the combination regimen ofazacitidine (75 mg/m², days 1-7) + venetoclax (400 mg, days 1-10 or days 1-14) combined with the GHApriming regimen (homoharringtonine 1 mg, days 1-7; low-dose cytarabine 10 mg/m², every 12 hours, days1-7; recombinant human granulocyte colony-stimulating factor 300 μg, days 1-7)...In terms of risk stratification at initial diagnosis, the favorable risk group accounted for32.1% (9/28), the intermediate risk group for 28.6% (8/28), and the poor risk group for 39.3% (11/28).Among them, 3 patients had AML1/ETO at initial diagnosis, 3 had CBFβ/MYH11, and 1 had BCR/ABL 190fusion gene, and this patient received dasatinib/imatinib during induction therapy... This prospective study confirms that the combination of azacitidine, venetoclax and GHApriming regimen can be an effective induction remission regimen for patients with refractory/relapsedacute myeloid leukemia, with high safety and good tolerance, which is..."

Clinical • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Febrile Neutropenia • Gastrointestinal Disorder • Hepatology • Infectious Disease • Liver Failure • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • Tuberculosis • CBFB

Venetoclax and Homoharringtonine-Based Therapy Exhibited a Striking Response in Refractory/Relapsed Early T-Cell Precursor Acute Lymphoblastic Leukemia. (PubMed, MedComm (2020)) - "Herein, we investigated the efficacy and safety of the V-HAG regimen (VEN, HHT, cytarabine, and granulocyte colony-stimulating factor [G-CSF]) in patients with refractory/relapsed ETP-ALL through a prospective, multicenter, single-arm, open-label, phase 2 clinical trial. The most common grade 3-4 adverse events were neutropenia (100%), anemia (88.9%), and thrombocytopenia (100%). Notably, the VEN- and HHT-based therapy, V-HAG regimen, exhibits an extremely high efficacy in the treatment of patients with refractory/relapsed ETP-ALL with good tolerance, and it provides a promising therapeutic strategy for improving their outcomes."

Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • T Acute Lymphoblastic Leukemia • Thrombocytopenia

Preclinical efficacy of the synergistic Ruxolitinib–Homoharringtonine combination in TP53-mutated myeloproliferative neoplasms progressing to sAML (ASH 2025) - "Neither JAKi monotherapy nor its combinations with standard AML regimens or with hypomethylating agents plus venetoclax have significantly improved outcomes for patients with MPN-EB, accelerated-phase (AP), or sAML. These findings demonstrate that the combination regimen of ruxolitinib and homoharringtonine exhibits significant preclinical activity against post-MPN sAML, particularly in patients harboring TP53 mutations, thus offering a promising strategy for future clinical application. Acknowledgement: This research was funded by the Zhejiang Provincial Health High-level Innovative Talent Project (2022-2026). *Correspondence to: Prof Jian Huang, E-mail:househuang@zju.edu.cn"

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • BAX • BCL2 • BCL2L1 • CASP3 • CCND1 • CDK2 • IL2 • IL6 • MYC • STAT3 • STAT5 • TP53

CHG combined with venetoclax and azacytidine as induction chemotherapy in acute myeloid leukemia (ASH 2025) - P2 | "Based on this premise, we endeavored to develop a low-dose, long-course CHG regimen (cytarabine, homoharringtonine, and granulocyte stimulating factor) in combination with the demethylating agent azacytidine and the Bcl-2 inhibitor venetoclax as an induction regimen(NCT06470841)...One patient achieved CRi after receiving daunorubicin plus cytarabine (DA) induction chemotherapy. However, the patient relapsed after completing 2 courses of consolidation chemotherapy (1 course of DA and 1 course of venetoclax + azacytidine + sorafenib)...In another patient, non-response (NR) was observed after 1 course of idarubicin plus cytarabine... In this trial, we utilized a low-dose, long-course regimen of CHG in combination with the demethylating drug azacytidine and the Bcl-2 inhibitor venetoclax as an induction regimen. Notably, all 5 patients achieved complete remission by a single course of VACHG induction chemotherapy, and the combined chemotherapy regimen demonstrated..."

Acute Kidney Injury • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Nephrology • Renal Disease

The efficacy and safety of homoharringtonine combined with venetoclax and azacitidine in primary refractory and relapsed/refractory acute myeloid leukemia (ASH 2025) - "Others received consolidation (VAH or high/intermediate-dose cytarabine) followed by maintenance as indicated. This study demonstrated high promising efficacy and safety of VAH regimen in primary refractory and relapsed/refractory AML patients, particularly in high-risk primary refractory and relapsed/refractory AML patients who were intolerant for intensive therapy. The VAH regimen significantly improved the response rates and overcome the negative impact of specific genetic patterns."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • ASXL1 • DNMT3A • FLT3 • IDH2 • RUNX1

AML1/ETO upregulates fatty acid metabolism to induce venetoclax resistance in acute myeloid leukemia via activation of c-myc/SCD1 pathway (ASH 2025) - "Several studies including ours demonstrate that AML1/ETO-positive acute myeloid leukemia (AML) has poor response to venetoclax (Ven) combined with azacitidine (AZA). Besides, our study showed the addition of homoharringtonine (HHT) to Ven/AZA significantly improved response...Altogether, our study highlighted an innorvative mechanism of FAM-mediated Ven resistance in AML1/ETO-positive AML and demostrated a promising strategy of adding HHT to overcome the resistance. Key words: AML1/ETO, fatty acid metabolism, c-Myc, SCD1, venetoclax"

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • MYC • SCD

A prospective study reveals feasibility and merits of drug profiling-guided precision therapy for children with high-risk leukemias (ASH 2025) - P | "Frequently useddrug combinations included chemotherapy plus venetoclax, homoharringtonine, or bortezomib.According to the best response per patient, 4 patients achieved complete remission (CR) and 3 achievedpartial remission (PR) while 5 patients had stable disease (SD), and 2 patients had progressive disease(PD)...Four patients (28.6%) hadactionable targets, including JAK2 in 2 patients, KIT in 1 patient, and FLT3-ITD in 1 patient, and only thepatient with FLT3-ITD received sorafenib as a matched therapy...In addition, the median TAT for returning genomic profiling results to the tumorboard was 30 days, which was significantly longer than that of drug profiling.Conclusions This study represents the largest case series with a pure cohort of pediatric acute leukemias to evaluatethe feasibility and merits of FPM, and demonstrated that FPM-guided therapy could achieve favorableresponses in pediatric patients with very high-risk leukemias, with a short TAT and high..."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • FLT3 • JAK2

Clinical study reveals the high efficacy and well-tolerance of venetoclax combined with homoharringtonine, azacitidine, and cytarabine in newly diagnosed AML (ASH 2025) - "Both the VAH and VAHA regimens achieve high CRc rates with well-tolerance in newlydiagnosed AML patients. Our results reveal that the VAHA regimen may act as the first-line treatment ofnewly diagnosed AML patients who are not suitable for intensive therapy."

Clinical • Acute Myelogenous Leukemia • B Cell Lymphoma • Infectious Disease • Leukemia • Lymphoma • Pneumonia • Respiratory Diseases • Septic Shock • BCL2 • CEBPA • DNMT3A • ENG • FLT3 • IDH2 • JUN • NPM1 • RUNX1 • TET2 • U2AF1