Reblozyl (luspatercept-aamt) / BMS, Merck (MSD) - LARVOL DELTA

Oral Arsenic (ATO) in Low-risk Myelodysplastic Syndromes (MDS) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Groupe Francophone des Myelodysplasies | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

DarbeLus: Luspatercept + Darbepoetin in MDS (clinicaltrials.gov) - P2 | N=54 | Not yet recruiting | Sponsor: Yale University

New P2 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

MAXILUS: A Study to Assess Luspatercept in Lower-risk Myelodysplastic Syndrome Participants (clinicaltrials.gov) - P3 | N=100 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Reblozyl: Data readout from P3 ELEMENT-MDS trial (NCT05949684) for non transfusion dependent MDS associated anemia in 2027 (Bristol-Myers Squibb) - Q2 2025 Results

P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

A Study to Evaluate Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Patients With Lower-Risk Myelodysplastic Syndromes Treated With Luspatercept (clinicaltrials.gov) - P=N/A | N=250 | Active, not recruiting | Sponsor: Bristol-Myers Squibb

HEOR • New trial • Real-world evidence • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Treatment Patterns and Outcomes in Patients With Lower-risk Myelodysplastic Syndromes Treated With Luspatercept in China (clinicaltrials.gov) - P=N/A | N=80 | Active, not recruiting | Sponsor: Bristol-Myers Squibb

New trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Luspatercept versus mitapivat for non-transfusion-dependent β-thalassemia: Dare to compare? (PubMed, Hemasphere) - No abstract available

Journal • Beta-Thalassemia • Genetic Disorders

Bristol Myers Squibb Announces Topline Results from Phase 3 INDEPENDENCE Trial for Reblozyl (luspatercept-aamt) in Adult Patients with Myelofibrosis-Associated Anemia (Bristol-Myers Squibb Press Release) - P3 | N=313 | INDEPENDENCE (NCT04717414) | Sponsor: Celgene | "Bristol Myers Squibb...announced the Phase 3 INDEPENDENCE trial evaluating Reblozyl (luspatercept-aamt) with concomitant janus kinase inhibitor (JAKi) therapy in adult patients with myelofibrosis-associated anemia receiving red blood cell (RBC) transfusions did not meet its primary endpoint of RBC transfusion independence during any consecutive 12-week period, starting within the first 24 weeks of treatment, compared to placebo (p=0.0674). Several important secondary measures also showed a clinically meaningful benefit favoring Reblozyl, which included a higher number of patients who achieved at least a 50% reduction (and by at least 4 RBC units) in RBC transfusion burden, as well as a higher number of patients achieving a hemoglobin (Hb) level increase by at least 1 g/dL while remaining transfusion independent for at least 12 consecutive weeks."

P3 data: top line • Anemia • Myelofibrosis

AZA-MDS-006: Connect® Myeloid Disease Registry (clinicaltrials.gov) - P=N/A | N=2013 | Terminated | Sponsor: Celgene | Trial completion date: Mar 2031 ➔ Oct 2024 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2031 ➔ Oct 2024; Business objectives have changed

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology

Current Landscape of Hepcidin Therapeutics. (PubMed, Adv Exp Med Biol) - "This chapter summarizes the current landscape of hepcidin therapeutics that reached clinical development and the pathologies that could benefit from these pharmacological approaches. Moreover, it provides novel experimental insights into new potential therapies combining hepcidin modulators with existing or novel approaches such as luspatercept or TfR2 targeting as a way to achieve further improvement of anemia in pathologic conditions."

Journal • Beta-Thalassemia • Genetic Disorders • Hematological Disorders

Efficacy and safety of luspatercept with or without erythropoiesis-stimulating agent in patients with myelodysplastic neoplasms with ring sideroblasts: A multicentre real-life study by the GFM. (PubMed, Br J Haematol) - No abstract available

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Luspatercept for Transfusion-Dependent Beta-Thalassemia: Real-World Experience in a Large Cohort of Patients From Italy. (PubMed, Am J Hematol) - No abstract available

Journal • Real-world evidence • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Hematological Disorders

RESEARCH ON THE EFFECT OF LUSPATERCEPT AND ERYTHROPOIETIN ON ERYTHROID DIFFERENTIATION IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (EHA 2025) - "Use Luspatercept, Roxadustat, and EPO for drug intervention in cell lines, and detect the effects of different drugs on the proportion of erythroid cells and the proportions of BFU-E and CFU-E.Hemin was used to induce erythroid transformation in K562 and KO cell lines. Our experimental results indicate that Luspatercept affects the morphological changes of KO cells during their differentiation into red blood cells, promotes the process of KO cells differentiating into mature red blood cells, and confirms its promoting effect on PNH erythroid transformation. The results of this experiment will have important reference significance for exploring the abnormal mechanisms of PNH erythroid differentiation."

Clinical • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • GYPA • TFRC

INDIVIDUALIZED AND INCLUSIVE STRATEGIES FOR TREATING JEHOVAH'S WITNESSES WITH ACUTE LEUKEMIA AND HIGH-GRADE MYELOID NEOPLASMS (EHA 2025) - "Treatments included: 7+3, attenuated decitabine+venetoclax, and azacitidine and sorafenib...One, treated with dasatinib+HyperCVAD, relapsed after 9 mos, then received Ponatinib+Blinatumomab, and underwent stem cell transplant...The third pt was treated with cyclophosphamide/topotecan for a co-occurring neuroblastoma without response, switching to blinatumomab then hospice due to neuroblastoma progression.For MDS - 1 pt received luspatercept for 8 mos before cessation due to cytopenia (Hgb of 2.9 g/dL)...TPO agonists included romiplostim at 2 to 4 mcg/kg weekly or daily eltrombopag, while G-CSF (Filgrastim, 5 mcg/kg) was administered based on ANC levels. Our study of Jehovah's Witness pts with acute leukemia and high-grade MDS underscores the possibility of individualized leukemia-directed care despite transfusion limitations. Despite significant baseline cytopenias, individualized treatment approaches and the use of hematopoietic growth factors can facilitate the..."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Neuroblastoma • Oncology • Septic Shock • Solid Tumor • NPM1

RELATIONSHIP BETWEEN HEMOGLOBIN AND QUALITY OF LIFE IN NON-TRANSFUSION-DEPENDENT PATIENTS WITH MYELOFIBROSIS TREATED WITH LUSPATERCEPT (EHA 2025) - "Pts in Cohorts 1 (no concomitant ruxolitinib [rux]) and 3A (on a stable dose of rux for ≥112 days prior to enrolment) of MF-001 were selected and pooled for this analysis. In pts with NTD MF treated with luspatercept, achieving a Hb level of ≥10 g/dL or increase of ≥1.5 g/dL was associated with a meaningful improvement in patient-reported anemia and fatigue symptoms. Most pts with a Hb response and evaluable QoL also experienced an improvement in anemia-related QoL. This analysis demonstrated a significant and clinically meaningful relationship between Hb increase and anemia-related QoL improvement in this population."

Clinical • HEOR • Anemia • Fatigue • Hematological Disorders • Myelofibrosis • Oncology

ANEMIA RESPONSE IN PATIENTS WITH MYELOFIBROSIS TREATED WITH LUSPATERCEPT: A REAL-WORLD COHORT STUDY (EHA 2025) - "The majority of patients (80%) were treated with a combination of JAK inhibitor with luspatercept; Ten (67%) patients received concomitant ruxolitinib, and 2 (13%) received concomitant momelotinib. Response rates in this real-world cohort of largely secondary MF treated with the luspatercept and JAK inhibitor combination are encouraging, despite the small sample size. Further dose optimization and identification of predictive response metrics are essential to better tailor luspatercept use for anemia in MF patients."

Clinical • Real-world • Real-world evidence • Anemia • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • CALR • JAK2 • TET2

LUSPATERCEPT FOR THE TREATMENT OF REFRACTORY ANEMIA IN MYELOFIBROSIS PATIENTS DURING RUXOLITINIB THERAPY (EHA 2025) - "This is a retrospective multicenter study aimed at evaluating the efficacy and safety of Luspatercept in MF patients with drug-resistant (include erythropoiesis-stimulating agents and androgens, or alternatively, corticosteroids, thalidomide, and other immunomodulatory drugs) refractory anemia during ruxolitinib therapy.The study included 48 MF patients with refractory anemia : 29 with PMF, 10 with post-PV MF, and 7 with post-ET MF. In patients with myelofibrosis, luspatercept improved refractory anemia during ruxolitinib therapy, the response to luspatercept was better,especially in the moderate anemia group,and with well tolerance."

Clinical • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • Pulmonary Disease • Thrombocytopenia

SINGLE CELL RNA-SEQ IDENTIFIES LUSPATERCEPT COULD SERVE AS A NOVEL THERAPEUTIC DRUG FOR APLASTIC ANEMIA (EHA 2025) - "Functional validation included flow cytometric apoptosis assays in PBMCs from SAA patients treated ex vivo with cyclosporine, eltrombopag, and luspatercept.Following 6 weeks of combination therapy, the patient achieved partial hematologic recovery without adverse events. The luspatercept-containing regimen demonstrates dual mechanisms of erythropoietic enhancement and immunomodulation, representing a promising therapeutic strategy for SAA. Dynamic scRNA-seq profiling and functional validation highlight its role in suppressing pathogenic immune activation, providing mechanistic insights for AA management."

Anemia • Aplastic Anemia • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Myelodysplastic Syndrome • Oncology • CD4 • CD8 • DUSP1 • S100A8 • TGFB1

EVALUATING INTERVENTIONAL TRIALS IN MYELOFIBROSIS-ASSOCIATED ANEMIA: A SYSTEMATIC LITERATURE REVIEW OF BASELINE ANEMIA STATUS AND TRANSFUSION INDEPENDENCE OUTCOMES (EHA 2025) - "Among the limited number of groups with reported baseline RBCT status (n=6), the TI rate was 14% in patients receiving ≤1 unit/month (ruxolitinib), 29-36% in those receiving 1-2 units/month (momelotinib), and 16-26% in those receiving 2-3 units/month (luspatercept and pomalidomide). This analysis examined the definitions of baseline anemia severity utilized in interventional trials and associated clinical outcomes in patients with MF-related anemia. Inclusion criteria for defining baseline transfusion burden varied based on Hgb thresholds, the number of transfused units, and the time period. Despite many MF patients becoming TD due to disease progression and treatment with JAKi, few trials focused on this hard-to-treat population, and treatment options remain limited for patients with a high transfusion burden."

Review • Anemia • Hematological Disorders • Myelofibrosis

IPSS-M risk and specific sex-associated somatic mutations predict response to ESA therapy in LR-MDS: building a new score. (PubMed, Blood) - "Despite the impact of IPSS-M score, no single mutated gene was linked to ESA response, however, when we stratified cases by sex at birth, we observed that mutations in the X-linked STAG2 gene were significantly associated with ESA resistance in LR-MDS males (OR 0.13, p=0.003). To our knowledge, this is the first study based on a large multicenter cohort of patients suggesting that the integration of IPSS-M score and sex-specific mutations can characterize erythropoiesis defects and guide first line therapeutic choices for anemic LR-MDS (i.e. ESAs vs Luspatercept)."

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • STAG2

A Kindred With Dominantly Inherited β-Thalassemia (Hemoglobin Chesterfield) Showing a Therapeutic Efficacy of Luspatercept. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal • Beta-Thalassemia • Genetic Disorders

Luspatercept in Transfusion-Dependent β-Thalassemia: The Benefit Is Real, and So Are the Risks. (PubMed, Am J Hematol) - No abstract available

Journal • Beta-Thalassemia • Genetic Disorders

CLINICAL STUDY ON THE EFFICACY AND SAFETY OF LUSPATERCEPT IN PATIENTS WITH MILD TO MODERATE ß-THALASSEMIA IN CHINA (EHA 2025) - "Luspatercept is an effective and well-tolerated treatment for adult patients with mild to moderate β-thalassemia in China. Further studies with larger sample sizes and extended follow-up are needed to assess its impact on serum ferritin level and spleen thickness."

Clinical • Anemia • Beta-Thalassemia • Fatigue • Genetic Disorders • Hematological Disorders

REGISTRY OF TRANSFUSION-DEPENDENT BETA-THALASSEMIA (TDT) CASES IN SPAIN MOLECULARLY CHARACTERIZED OVER THE PAST 20 MONTHS (EHA 2025) - "Fourteen were treated with luspatercept... The phenotype of the mutations determines the frequency of transfusions in patients with β-thalassemia TDT, with mutations such as CD39 (C>T) or IVS-1-nt1 (G>A) strongly associated with the need for regular and frequent transfusions due to their disruptive nature. Most patients are treated with iron chelators, mainly deferasirox, though some require a combination of chelators, indicating a high iron load or suboptimal response to standard treatment. The diversity of genotypes and variability in transfusion needs highlight the complexity of managing this condition and the necessity for individualized treatment strategies."

Clinical • Beta-Thalassemia • Genetic Disorders • ENTPD1 • HBA2

CLINICAL STUDY ON THE EARLY EFFICACY AND SAFETY OF LUSPATERCEPT IN TREATING ANEMIA IN PATIENTS WITH MYELOFIBROSIS (EHA 2025) - "Eligible patients must have received < 12 units of red blood cell (RBC) transfusion within 12 weeks before enrollment and undergone at least one anemia treatment (including EPO, androgens, thalidomide/lenalidomide, or glucocorticoids), with a hemoglobin (Hb) level ≤ 8 g/dL prior to RBC transfusion. This study preliminarily shows that adding luspatercept at 1.33 mg/kg to current treatments can improve anemia in some MF patients in the short term, with a good safety profile. Further studies of a larger sample size and with extended follow-up are needed to investigate its long-term efficacy and safety."

Clinical • Anemia • Fatigue • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Nephrology • Oncology • Renal Disease • Thrombocytopenia • TGFB1