Elzonris (tagraxofusp-erzs) / Menarini, Nippon Shinyaku - LARVOL DELTA

Tagraxofusp and low-intensity chemotherapy for the treatment of CD123-positive relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Background and Significance: The combination of venetoclax and a hypomethylating agent (Ven/HMA) is the standard frontline (1L) therapy for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (IC)...Cladribine (CLAD) with low-dose cytaratbine (LDAC) has previously been shown to be well-tolerated and effective in IC-ineligible patients with newly diagnosed AML...The study began enrolling patients in January 2025 and is actively recruiting. Clinical Trial Registration NCT06561152"

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • BCL2 • CD123 • IL3RA

Single center retrospective evaluation of CHOP-based regimens in older patients with treatment naive blastic plasmacytoid dendritic cell neoplasm (ASH 2025) - "In this series, the major driver in improvement in overall survival difference appears to be younger age and ability to proceed to allo-HCT. Although limited by retrospective design and small number of patients, this study suggests CHOP-based induction strategies achieve remission rates similar to those obtained with tagraxofusp-erzs for treatment naïve BPDCN and may be considered as a potential frontline therapy for older patients with BPDCN."

Retrospective data • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • CD123 • IL3RA

Plasmacytoid dendritic cell-associated acute myeloid leukemia (pDC-AML) a comprehensive review (ASH 2025) - "Treatments include induction chemotherapy, hypomethylating agents (e.g., azacytidine plus venetoclax), and allogeneic hematopoietic stem cell transplantation (allo-HSCT)...Emerging therapies targeting CD123 (e.g., tagraxofusp) and immune-modulating agents are under investigation... pDC-AML is a clinically aggressive and biologically distinct AML subtype defined by clonal pDC expansion, frequent RUNX1 mutations, and suboptimal responses to current therapies. Accurate diagnosis relies on integrated immunophenotypic and genetic profiling. Despite progress, patient outcomes remain poor, underscoring the need for improved classification, prognostic markers, and targeted therapeutic strategies."

Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • ASXL1 • BCOR • CD123 • CD34 • CLEC4C • DNMT3A • FLT3 • IL3RA • KIT • NCAM1 • NRP1 • RUNX1 • SRSF2 • TCL1A • TET2

From juvenile idiopathic arthritis to blastic plasmacytoid dendritic cell neoplasm: A diagnostic odyssey in a 14-year-old patient (ASH 2025) - "The patient was treated with standard therapy including methotrexate and adalimumab...Novel therapeutics targeting CD123, such as tagraxofusp (SL-401), a CD123-directed cytotoxin, have shown high response rates in adult populations, yet pediatric efficacy and safety data remain limited. Other investigational agents includes, venetoclax and CD123-directed CAR-T cells... This case emphasizes the urgent need for increased awareness of BPDCN in pediatric practices, given it is bimodal distribution. Earlier diagnostic consideration in atypical autoimmune presentations and expanded access to pediatric-specific treatment protocols and clinical trials are critical keys for improving outcomes in such vulnerable population."

Clinical • Hematological Malignancies • Idiopathic Arthritis • Immunology • Lymphoma • Mucositis • Musculoskeletal Diseases • Musculoskeletal Pain • Non-Hodgkin’s Lymphoma • Orthopedics • Rheumatology • CD123 • CD4 • CLEC4C • IL3RA • NCAM1

Real-world use of venetoclax and hypomethylating agents (HMA) in blastic plasmacytoid dendritic cell neoplasm (BPDCN): A multi-institutional case series (ASH 2025) - "Introduction:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancyoriginating from plasmacytoid dendritic cell precursors, historically associated with poor patientoutcomes. Ven+HMA shows encouraging activity in BPDCN, including in R/R cases, with a high ORR similar toTagraxofusp in the R/R setting. However, relapses involving CNS or EMD were common, highlighting theneed for improved CNS surveillance and prophylaxis. Although limited by its retrospective design andsmall sample size, these real-world findings support continued evaluation of Ven+HMA, particularly infrontline and combination regimens."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • ASXL1 • DNMT3A • IKZF1 • JAK2 • NRAS • TET2 • ZRSR2

Poor survival and temporal trends in blastic plasmacytoid dendritic cell neoplasm: A SEER 2000–2022 analysis (ASH 2025) - "However, population-based data on incidence and survival trendsremain limited, particularly in the era of novel agents such as tagraxofusp...BPDCN predominantly affects older males and continues to carry poor survival despite highchemotherapy utilization. Worsening survival trends and limited radiation benefit underscore the needfor optimized therapeutic strategies, improved data capture on novel agents, and equitable access toemerging treatments.Impact Statement:This is the first SEER-based study to comprehensively evaluate temporal survival trends, treatmentpatterns, and demographic disparities in BPDCN over two decades.Limitations:SEER lacks information on stem cell transplantation, novel targeted therapy use, and performance status,which may influence outcomes."

Hematological Malignancies

Favorable outcomes including post-transplant survival are seen independent of baseline skin burden in treatment-naïve patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG): Subgroup analysis of a pivotal Trial (ASH 2025) - P1/2 | "Furthermore, the comparablesafety profile and, notably, the reduced incidence of grade 3-4 CLS in the high mSWAT group areimportant clinical observations. These results confirm TAG is an effective 1L therapy irrespective ofdisease burden or clinical presentation, and serves as the standard of care in all eligible pts with BPDCN."

Clinical • Post-transplantation • Dermatology • Hematological Malignancies • Transplantation • CD123 • IL3RA

Longer survival with tagraxofusp versus venetoclax in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Results of a real-world analysis (ASH 2025) - P1/2 | "Importantly, more pts were able to receive a subsequentline of therapy after TAG-based regimens. These results support the use of TAG as first-line standard ofcare therapy for both transplant-eligible and transplant-ineligible pts with BPDCN."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Cardiovascular • Diabetes • Hematological Malignancies • Peripheral Arterial Disease • Pulmonary Disease • Respiratory Diseases • CD123 • IL3RA

Real-world study of treatment landscape and safety outcomes of US patients with blastic plasmacytoid dendritic cell neoplasm (ASH 2025) - "Currently, tagraxofusp (Tag) is the only FDA-approved therapy for BPDCN (2018), althoughcombination treatment with other antineoplastic agents occurs in clinical practice (Pemmaraju et al.,2023)...Among LoT1patients (n=551, 69%), 61% were treated with steroid monotherapy, 4% with Tag (with or withoutsteroids), and 34% with other agents (eg, venetoclax + hypomethylating agents; cyclophosphamide,hydroxydaunorubicin, oncovin, and prednisone [CHOP]; etc.)... This RW study highlights the limited treatment options and durability of currently availablePTs for BPCDN. Of note, these RW data also show a high percentage of PCHM and solid tumors withBPDCN and should be explored further. While dx codes in claims may misclassify clinical features and AEincidence, application of medication and procedure codes define LoT more accurately than EHR dataalone."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • B Cell Lymphoma • Breast Cancer • Chronic Myelomonocytic Leukemia • Chronic Obstructive Pulmonary Disease • Diabetes • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lung Cancer • Lymphoma • Myelodysplastic Syndrome • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia

A Trial Designed to Learn as well as Treat (PRNewswire) - "This phase 1/2 trial (NCT07148180) is now active at Dana-Farber Cancer Institute and will be jointly conducted across four of Break Through Cancer's clinical centers including Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins."

Trial status • Acute Myelogenous Leukemia

Khsrp depletion selectively eliminates AML cells that persist after venetoclax/azacitidine therapy via modulating SLC23A1-transported TET enzyme cofactors (ASH 2025) - "Two regimens were tested,venetoclax plus azacitidine (VEN/AZA) and tagraxofusp, each at its IC90 dose, to explore shared targets inresidual disease. We are currentlyevaluating the effects of KHSRP depletion in prolonging survival of two independent AML in vivo modelstreated with VEN/AZA. These data nominate KHSRP as a selective vulnerability in therapy-persistent AMLand warrant the development of KHSRP inhibitors to target residual disease."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Solid Tumor • CD123 • IL3RA • SLC23A1 • TET2

Tagraxofusp, azacitidine, and venetoclax (TAG-AZA-VEN) triplet therapy shows efficacy, tolerability, and transplant potential in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Results of a phase 2 trial (ASH 2025) - P1 | "Triplet therapy with TAG-AZA-VEN is effective and feasible in patients with previouslyuntreated or R/R BPDCN, including in an older patient population. The safety profile is consistent withprior studies of TAG and AZA/VEN, and triplet therapy does not add new AEs not seen with TAG orAZA/VEN. A high proportion of patients (1L and R/R) proceeded to transplant in remission."

Clinical • IO biomarker • P2 data • Atrial Fibrillation • Cardiovascular • CNS Disorders • Diabetes • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Renal Disease • Thrombocytopenia • Transplantation • BCL2 • CD123 • IL3RA

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) international registry: Assessment of the allo-HCT outcomes (ASH 2025) - P | "Initial treatment has utilized ALL-based regimens in 12 patients and included Hyper-CVAD (n=6),cytarabine/idarubicin/VP16 (n=1), ALL-IC BFM 2009 (n=3), GMALL (n=1), EPOCH (n=1)...Second line therapy was used in all patients, with gemcitabine/oxaliplatin/dexamethasoneregimen (n=1), venetoclax/azacytidine (n=1), venetoclax monotherapy (n=1) and SL-401 clinical trial (n=1)․First two patients experienced stable disease (SD) with duration of 72 and 4 months respectively, theother two were alive at last contact.As of the last follow- up, 10 (63%) patients were alive with median follow-up of 27 months (range 8-146months)... The data confirmed the efficacy of allo-HCT in patients with BPDCN. Our previously reporteddata highlighted the importance of allo-HCT for the tagraxofusp group, as outcomes were less favorablein those who did not undergo allo-HCT. Based on current evidence, we conclude that optimizing accessto tagraxofusp followed by allo-HCT may offer the best..."

Bone Marrow Transplantation • Hematological Disorders • Leukopenia • Rare Diseases • Thrombocytopenia • CBLC • CD123 • CD2AP • CD4 • CLEC4C • DNMT3A • IL3RA • NCAM1 • TET2

Roswell Park Experts Share Latest Hematology Research at 67th ASH Annual Meeting (Roswell Park Comprehensive Cancer Center)

Clinical data • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Blastic Plasmacytoid Dendritic Cell Neoplasm • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Multiple Myeloma

Menarini Group Announces New Data on ELZONRIS (tagraxofusp-erzs) to be Presented at the 67th American Society of Hematology Annual Meeting and Exposition (PRNewswire) - "The presentations include an oral session highlighting results from a triplet therapy combining tagraxofusp, azacitidine, and venetoclax, which demonstrated both efficacy (high response and bridge to transplant rates) and tolerability in individuals with blastic plasmacytoid dendritic cell neoplasm (BPDCN)."

Clinical data • Blastic Plasmacytoid Dendritic Cell Neoplasm

Tagraxofusp Shows Promising Anti-Tumoral Efficacy in Preclinical in Vitro Models of Myelofibrosis, Both As a Single Agent and in Combination with Janus Kinase Inhibitors (ASH 2023) - P1/2 | "The role of the JAK/Signal transducer and activator of transcriptions (STAT) pathway in MF has led to the recent approval of three different JAK2 inhibitors (ruxolitinib, pacritinib, and fedratinib) for MF treatment. Our studies showed high sensitivity of MF cell lines to tagraxofusp as a single agent, which is expected given phase 2 results demonstrated clinical efficacy of single-agent tagraxofusp in R/R MF (Yacoub et al. ASH 2021). In addition, synergism was observed in combination with JAK inhibitors."

Combination therapy • Preclinical • Hematological Malignancies • Infectious Disease • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • CD123 • IL3RA

Tagraxofusp Maintenance Post-Hematopoietic Stem Cell Transplantation Provides Long-Term Survival and Manageable Safety for a Patient with Blastic Plasmacytoid Dendritic Cell Neoplasm (ASH 2023) - P2 | "Therapy prior to allo-HCT included hydroxyurea and TAG + venetoclax + mini-HyperCVAD for 5 cycles. This case report demonstrates a patient experiencing a clinically meaningful benefit with TAG maintenance therapy after allo-HCT. Both prolonged survival and manageable safety, in this case, highlight the feasibility of long-term TAG maintenance post-allo-HCT to control BPDCN."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation • CD123 • IL3RA

Analysis of Tagraxofusp Activity in AML-Pdc As a Single Agent and in Combination with BCL2 Inhibitors (ASH 2023) - "Tagraxofusp was able to effectively eliminate pDCs and blasts to a lesser extent as a single agent. High expression of BCL-2 in blasts supports the consideration of tagraxofusp in combination with venetoclax as an effective combination therapy to eradicate both blasts and pDCs in AML-PDC patient samples."

Combination therapy • IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • CD123 • CD34 • IL3RA • STAT5

Phase 2 Multicenter Trial of Tagraxofusp in Combination with Venetoclax and Azacitidine in Adults with Previously Untreated CD123+ Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy (ASH 2024) - P2 | "Genomic profiling and CD123 expression will be analyzed at baseline and during study treatment. Part 1 will enroll patients from North America, S Korea & Australia."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Oncology • CD123 • IL3RA • TP53

Results of a Phase I/II Study of Tagraxofusp in Combination with Decitabine for Patients with Myelodysplastic/Myeloproliferative Neoplasms and Higher Risk Myelodysplastic Syndromes (ASH 2024) - "One patient (11%) had received prior allogeneic stem-cell transplantation and 1 (11%) had received prior HMA-venetoclax therapy...Both events occurred in patients >75 years of age during cycle 1 of therapy and reverted to baseline (< grade 1) with appropriate management including steroids, albumin and furosemide. One patient received a single dose of tocilizumab...Although TAG at low doses is associated with acceptable safety profile with no new safety signals, CLS and CRS can be observed in older patients. Further follow up and enrollment is ongoing in younger (<75 years of age) patients to confirm the long-term efficacy and safety of this combination."

Clinical • Combination therapy • P1/2 data • Atrial Fibrillation • Cardiovascular • Chronic Myelomonocytic Leukemia • Constipation • Cough • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • CD123 • IL3RA • TP53

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Series and Review of Literature. (PubMed, Cureus) - "The first-line treatment in one patient was tagraxofusp, followed by allogeneic stem cell transplant. The second patient was treated with venetoclax in monotherapy. The third patient was treated with a combination of venetoclax and intensive chemotherapy followed by allogeneic stem cell transplant as a consolidating therapy."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • Transplantation

Treatment Approaches for Blastic Plasmacytoid Dendritic Cell Neoplasm: Data from the Pethema and PALG Epidemiologic Registry (ASH 2024) - "This includes the CD33 or CD123 targeted molecules, as tagraxofusp, which has demonstrated activity as a front-line therapy...Among intensive treatment group, 45 (34%) received AML-like (34 with 3+7, 9 FLAG-IDA, and 2 HAM); 60 (46%) ALL-like (55 HyperCVAD and 5 with PETHEMA-ALL), and 27 (20%) lymphoma-like (17 CHOP, 7 etoposide-based, 1 ABVD, and 2 bortezomib-based). The non-intensive group included 21 (40%) AML-like regimens (10 AZA, 5 AZA-VEN, 4 LDAC, and 2 fludarabine+LDAC); 18 (34%) CD123 or CD33 targeted molecules, 9 (16%) ALL-like therapies (vincristine and dexamethasone-based), and 5 (10%) lymphoma-like, including 3 with radiotherapy or intralesional chemotherapy...The differences between treatment subgroups, such as age at diagnosis, among others, could influence the differences in OS. Larger studies and observational protocols are needed to identify best upfront regimens for BPDCN."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD123 • IL3RA

Single Agent Tagraxofusp in Relapsed/Refractory CD123-Positive Acute Myeloid Leukemia: A Preliminary Analysis of Italian Gimema AML2020 Trial (ASH 2023) - P2 | "First-line treatment consisted of fludarabine-based induction, CPX-351, conventional anthracycline/Ara-C (3+7) induction for 22 patients and 1 patient received reduced intensity induction with hypomethylating agents + venetoclax. Second line treatments included azacytidine, azacytidine + venetoclax, gilteritinib; six patients received TAG as second line treatment... These results show that single agent TAG can exert anti-leukemic activity in R/R CD123-positive AML, even in cases with very unfavourable prognosis. However, further studies are necessary to disclose predictors of response and of the risk of adverse events. The safety profile observed here is similar to that previously observed for TAG requiring close monitoring of patients and timely supportive measures."

Acute Kidney Injury • Acute Myelogenous Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Infectious Disease • Leukemia • Oncology • Renal Disease • Systemic Inflammatory Response Syndrome • CD123 • IL3RA

Evaluation of Treatment Outcomes in Adults with Blastic Plasmacytoid Dendritic Cell Neoplasm: A Systematic Review and Meta-Analysis (ASH 2023) - " We identified 818 total patients: 36% (292/818) received tagraxofusp, 60% (494/818) received intensive chemotherapy (HyperCVAD, AML and ALL-like, and CHOP), 3% (22/818) received less intensive chemotherapy (azacytidine, venetoclax, or other mild regimes), 1% received pivekimab (10/818). From our analysis, the OR of attaining CR between tagraxofusp and chemotherapy was not significant and did not answer the question of which modality has a higher chance of CR. Although it is not possible to draw a direct comparison between the pooled single arm trials, the trend of proportions favored tagraxofusp for obtaining both CR (71% vs 64%) and PR (17% vs 8%). While the mortality rate was higher for tagraxofusp compared to intensive chemotherapy (43% vs 30%), the NR rate (~21%) and the allo-HSCT rate (~50%) were similar."

Retrospective data • Review • Bone Marrow Transplantation • Rare Diseases • Transplantation • CD123 • IL3RA

Spatial Response to Pivekimab Sunirine (IMGN632) In Vivo in a BPDCN Model (ASH 2023) - "Standard of care treatments for BPDCN patients are intense chemotherapy or tagraxofusp (Elzonris®)...Pivekimab sunirine was granted orphan drug and Breakthrough Therapy designation and is currently being tested for the treatment of BPDCN patients as monotherapy and, as a triplet therapy in combination with azacitidine and venetoclax for the treatment of AML patients...Pivekimab sunirine is a potent ADC targeting CD123 and is highly efficacious against an aggressive BPDCN cell line model. This finding reinforces the importance of its use for the treatment of BPDCN patients."

Preclinical • Hematological Malignancies • Oncology • CD123 • IL3RA