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

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

Homoharringtonine added to CLAG regimen improves outcome of pediatric Relapsed/Refractory AML: A multicenter prospective study (ASH 2025) - P4 | "All patients had received CHAG regimens for salvage chemotherapies asfollows: cladribine (5mg/m2/day, day 1-5), HHT (1mg/m2/day, day 1-14), cytarabine (10mg/m2, quaque 12hora, day 1-14), granulocyte colony-stimulating factor (200ug/m2/day, day1-14) (cycle 1). The most common nonhematologic toxicities were febrileneutropenia, mostly assessed as grade 3 to 4, and not life-threatening.ConclusionIn summary, this trial showed that CHAG regimen is safe and highly active in R/R AML children. The CHAGregimen may represent a highly promising bridging strategy to allo-HSCT in pediatric R/R AML."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Neutropenia • Pediatrics • FLT3 • KMT2A • RUNX1 • RUNX1T1

Molecular subtype combined with peripheral blast clearance rate to optimize the treatment of newly diagnosed Acute Myeloid Leukemia: Interim analysis of the multicenter, Phase II study (IA+X 2024) (ASH 2025) - P2 | "For patients inthe D5-PBCR (+) group, addition of homoharringtonine can benefit favorable and intermediate riskgroups. While for adverse-risk and FLT3-ITD mutated cases, other interventions were needed.Patients and IA+X 2024 is a multicenter, non-randomized, phase II clinical trial, conducted to evaluate the efficacy oftargeted drug (drug "X") in combination with "3+7" regimen for ND-AML (ClinicalTrials.gov NCT06652685).Patients receive IA-10 regimen (idarubicin 10mg/m2 on days 1–3 and cytarabine 100mg/m2 on days 1–7)as the initial induction...All other D5-PRCR (+) patients will receive Venetoclax(VEN) addition (induction: 100mg on day 6, 200mg on day 7, and 400mg on days 8–13; consolidation:400mg/d on days 8-14).The primary end point is composite complete remission (CRc) rate...FLT3-ITD mutated patients (15 in ITT and 12 in PP) showedhigh response with IA+gilteritinib, which is also observed in patients with NUP98 fusion... The IA+X 2024..."

Clinical • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CBFB • FLT3 • NPM1 • NUP98 • RUNX1 • RUNX1T1 • TP53

Genetic risk stratification in adults with AML receiving venetoclax-based intensive therapy: A real-world study (ASH 2025) - "Therapy regimens included venetoclax withor without a hypomethylating agent (VEN±HMA), combined with one of the following:homoharringtonine-based therapy, anthracycline-based regimens, purine analog-containing regimens, orintermediate-/high-dose cytarabine-based protocols. The model was further verified in an external validation cohort.In concclusion, the ICV-CHN model offers a molecularly grounded and clinically applicable riskstratification framework for AML patients undergoing VEN-intensive therapy. This model enhancesoutcome prediction beyond current ELN classifications and may support more personalized treatmentapproaches in real-world settings."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CEBPA • FLT3 • KMT2A • NPM1 • RUNX1 • RUNX1T1 • TP53

Adult acute myeloid leukemia with NUP98 rearrangement benefits from targeted therapy and bone marrow transplantation (ASH 2025) - "According to ELN 2022 risk classification, 55 (77.5%) wereat intermediate risk and 16 (22.5%) at adverse risk.The induction therapy was divided into two types: targeted agents-based therapy (including Venetoclaxor Gilteritinib, combining with low-intensity or intensive chemotherapy, however Menin inhibitors havenot been available in China till now) or traditional chemotherapy (including 7+3, hypomethylation agents(HMA), Homoharringtonine-based therapy, et al.). Adult AML with NUP98 rearrangement should be recognized as one of adverse risk subgroups,irrespective of different fusion partners. Targeted therapy had higher chance of achieving CRc, and bonemarrow transplantation in CR1 was the key to long-term survival."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Transplantation • BCL2 • FLT3 • HOXA13 • HOXA9 • NSD1 • NUP98

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

CDK7 enables adaptive gene transcription required by stromal cells to support distinct T-cell lymphoma phenotypes and represents a novel microenvironment-directed therapeutic target (ASH 2025) - "Among these, ten drugs including the XPO1 inhibitor Selinexor, the HSP90 inhibitor PU-H71 andthe translation inhibitor Omacetaxine exhibited enhanced anti-lymphoma activity specifically in the co-culture setting, whereas four compounds showed reduced efficacy. Treatment with YKL-5-124significantly reduced the tumor burden compared to vehicles. Cytokine profiling (immunoblotting array)and ELISA of culture medium of YKL-5-124 treated EL4-CAFs showed reduced levels of pro-inflammatorycytokines such as CXCL12, IL6, CCL2, ICAM-1, and CXCL1 indicating that CDK7 is necessary in establishingpro-lymphomagenic IN-CAF phenotypes.In conclusion, CDK7 activity is required to sustain specific pro-tumoral crosstalk interactions of matchedCAFs and PTCL cells, which can be exploited therapeutically."

IO biomarker • Stroma • Hematological Malignancies • Lymphoma • T Cell Non-Hodgkin Lymphoma • CAFs • CCL2 • CDC37 • CDK7 • COL1A1 • COL1A2 • CXCL1 • CXCL12 • CXCR4 • EIF4E • ICAM1 • IL6 • MMP8

Targeting CPNE8 suppresses HOXA9-dependent AML progression and overcomes chemotherapy resistance (ASH 2025) - "CPNE8-high PBMCs showed significantly elevated IC50 values across a range of clinicallyrelevant chemotherapeutics, including idarubicin, homoharringtonine, fludarabine, azacitidine,venetoclax, aclarubicin, all-trans retinoic acid (ATRA), and mitoxantrone. Importantly, both Menin inhibition and CPNE8 knockdown prolonged survival in CPNE8-high AMLxenograft models, underscoring their therapeutic potential.ConclusionCPNE8 functions as a critical downstream effector of HOXA9, driving AML progression and therapyresistance through activation of Rap1 signaling, reprogramming of mitochondrial metabolism, andreshaping of the immune microenvironment. Blocking the HOXA9–CPNE8–Rap1 pathway, especially withMenin inhibitors, provides a rationale for stratified treatment strategies in CPNE8-high AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • HOXA9

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

Disrupting monocytic AML and monocytic leukemia stem cells with a novel cladribine regimen: From bench to bedside (ASH 2025) - P2 | "2023); (2)Homoharringtonine (HHT), a clinical agent widely used in China that efficiently degrades MCL1 highlyexpressed in monocytic blasts; and (3) Cytarabine (AraC), the standard chemo backbone...We first compared the efficacy of the CHA combination and venetoclax/azacitidine (Ven/Aza) in the Ven-resistant mono-AML cell line THP1 in vitro and in THP1-derived xenograft models in vivo...We propose a novel and effective CHA regimen thatis readily applicable in the clinic and demonstrates the ability to disrupt mono-LSCs and mono-AML. Aclinical trial evaluating an alternating Ven/Aza and CHA regimen is currently in development."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • BCL2 • FLT3 • GLI2 • MCL1 • NPM1 • RAS • TP53

Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: University of Colorado, Denver | Trial primary completion date: Aug 2026 ➔ Oct 2025

Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

The Pharmacological Atlas of Meningiomas (SNO 2025) - "The top five drugs with the lowest IC50 values were romidepsin, dactinomycin, carfilzomib, plicamycin, and omacetaxine, with median values of 10, 31, 145, 303, and 400 nM, respectively. Considering the ratio of peak serum concentration (Cmax) to IC50 as a potential predictor of treatment efficacy (>1), the HDAC inhibitors belinostat (74.5), romidepsin (69.7), along with the proteasome inhibitor carfilzomib (34.6), and the anthracyclines epirubicin (2.6), and doxorubicin (1.8), and the PI3K inhibitor idelalisib (1.6) are the most promising drug candidates for further evaluation. This study offers the first comprehensive insight into the pharmacological landscape of meningiomas, providing a crucial foundation for future clinical trials aimed at developing systemic treatments for aggressive meningiomas."

Brain Cancer • Meningioma • Solid Tumor

Extensive myeloid sarcoma presenting with esophageal compression and dysphagia as the initial manifestation. (PubMed, Medicine (Baltimore)) - "Infiltrative mediastinal/retroperitoneal MS may present with esophageal obstruction and mimic lymphoma or carcinoma. High-index suspicion, targeted biopsy with high-power morphology, and a focused immunohistochemical panel are critical for timely diagnosis and treatment initiation."

Journal • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Sarcoma • Solid Tumor • CD2 • CD20 • CD34 • CD5 • CD7 • CD79A • CD99 • CK19 • KIT • KRT19 • PTPRC

A preliminary analysis of the efficacy and safety of homoharringtonine, venetoclax, and azacitidine for newly diagnosed acute myeloid leukemia (PubMed, Zhonghua Xue Ye Xue Za Zhi) - "Treatment regimen (VHA vs VA) , MRD negativity after the first cycle, and receipt of transplantation were independent prognostic factors for OS. VHA provides clinical benefit in newly diagnosed AML patients who are unfit for intensive chemotherapy and in older adults, with particularly favorable outcomes in high risk patients; sequential allo-HSCT confers additional benefit, and associated adverse events are manageable."

Journal • Retrospective data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia • Transplantation

Sorafenib Plus Triplet Therapy with Venetoclax, Azacitibine and Homoharringtonine for Refractory/Relapsed Acute Myeloid Leukemia with FLT3-ITD: A Multicentre, Phase 2 Study (ASH 2023) - "We aimed to investigate the activity of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as salvage therapy for this population. Conclusions Sorafenib plus VAH regimen is well tolerated and highly active for R/R AML with FLT3-ITD. This regimen might be a suitable therapeutic option for this population, and larger population trials are needed to be explored."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia

Azacitidine, Homoharringtonine and Cytarabine Combined with Granulocyte Colony-Stimulating Factor As Frontline Treatment for Older Patients with Acute Myeloid Leukemia: A Prospective, Multicenter, Single-Arm Phase III Study in China (ASH 2024) - "A number of novel treatments are therefore being explored, such as DNA hypomethylating agents (HMAs) and B-cell leukemia/lymphoma-2 (BCL-2) inhibitor and gemtuzumab ozogamicin. Conclusions : Azacitidine combined with HAG regime is effective and well tolerated in older, medically unfit patients with acute myeloid leukemia. More randomized control clinical trials are needed to confirm the advantages of this regimen over venetoclax combined with azacytidine."

P3 data • Acute Myelogenous Leukemia • Anemia • Cerebral Hemorrhage • Infectious Disease • Lymphoma • Neutropenia • Respiratory Diseases • Thrombocytopenia • ENG

Homoharringtonine Shows Efficacy Against Melanoma Leptomeningeal Disease in Preclinical Models Using Patient-Derived Tumor Cells (SNO 2025) - "Among the most potent were ponatinib (EC₅₀: 1.85–4.06×10⁻⁶), sorafenib (9.57–9.77×10⁻⁶), ceritinib (1.84–2.05×10⁻⁶), and homoharringtonine (HHT; 3.63–4.11×10⁻⁸). This study introduces a robust preclinical platform for identifying effective treatments for M-LMD. Our findings highlight the promise of repurposing FDA-approved HHT as a therapeutic option. Future work will focus on elucidating HHT's molecular mechanisms and testing its efficacy across other LMD subtypes, such as those arising from breast and lung cancers."

Preclinical • Tumor cell • Breast Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • CTCs

In Vitro Drug Sensitivity and Clinical Efficacy of the HAG Regimen in Pediatric AML. (PubMed, Oncologist) - "The HAG regimen demonstrates high efficacy and holds great promise for pediatric AML. It achieves survival outcomes comparable to more intensive regimens while offering the significant advantage of reduced toxicity."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Visualizing the translation landscape in human cells at high resolution. (PubMed, Nat Commun) - "Finally, high-resolution structures from cells treated with homoharringtonine and cycloheximide revealed a distinct translational landscape and a spermidine that interacts with cycloheximide at the E site, one of the numerous polyamines that also bind native ribosomes. These results underscore the value of high-resolution in situ studies in the native environment."

Journal

Homoharringtonine Shows Efficacy Against Melanoma Leptomeningeal Disease in Preclinical Models Using Patient-Derived Tumor Cells (WFNOS 2025) - "Among the most potent were ponatinib (EC₅₀: 1.85–4.06×10⁻⁶), sorafenib (9.57–9.77×10⁻⁶), ceritinib (1.84–2.05×10⁻⁶), and homoharringtonine (HHT; 3.63–4.11×10⁻⁸). This study introduces a robust preclinical platform for identifying effective treatments for M-LMD. Our findings highlight the promise of repurposing FDA-approved HHT as a therapeutic option. Future work will focus on elucidating HHT's molecular mechanisms and testing its efficacy across other LMD subtypes, such as those arising from breast and lung cancers."

Preclinical • Tumor cell • Breast Cancer • Lung Cancer • Melanoma • Solid Tumor • CTCs