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

Overexpression of the TGF-β target CCN2 in megakaryocytes: a common feature of MDS with mutated SF3B1 : Uncovering novelinsights into the bone marrow microenvironment in MDS. (PubMed, Virchows Arch) - "In aggregate, these findings may contribute to a better understanding of disease pathophysiology and help elucidate the role of potentially clinically relevant TGF-β signaling. This is particularly significant given the clinical use of agents targeting TGF-β-signaling such as luspatercept, as well as the emergence of several CCN2-targeting therapies currently undergoing clinical or preclinical evaluation with promising results."

Journal • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ASXL1 • CTGF • RUNX1 • SF3B1 • TGFB1

Clinical benefit of luspatercept in erythropoiesis-stimulating agent (ESA)-naive patients (pts) with early disease characteristics and very low-, low-, or intermediate-risk Myelodysplastic Syndromes (LR-MDS): A post hoc analysis from the commands trial (ASH 2025) - P3 | "Background :In the phase 3 COMMANDS trial (NCT03682536) evaluating pts with ESA-naive transfusion-dependent(TD) LR-MDS, luspatercept was superior to epoetin alfa (EA) in achieving red blood cell-transfusionindependence (RBC-TI) ≥12 weeks (wks) and demonstrated a more durable clinical benefit. Pts with less severe disease characteristics, reflective of an earlier disease stage, derive greater clinicalbenefit from treatment than those with more advanced characteristics. Pts on luspatercept vs EAdemonstrated higher response rates and longer duration of response regardless of disease stage, furthersupporting its role as a preferred first-line therapy in LR-MDS."

Clinical • Retrospective data • Hematological Malignancies • Myelodysplastic Syndrome

A Trial Comparing Three Different Treatment Options for Adults With Low-Risk Myelodysplasia and Anemia (A MyeloMATCH Treatment Trial) (clinicaltrials.gov) - P2 | N=270 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P2 trial • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis. (PubMed, Blood Adv) - P2 | "The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non-transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); patients in cohort 3A/3B had stable ruxolitinib treatment prior to and during the study. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. NCT03194542 clinicaltrials.gov."

Journal • Anemia • Cardiovascular • Hematological Disorders • Hypertension • Myelofibrosis

Real-world evidence supports the safety and efficacy profile of luspatercept in clinically complex and heavily iron-overloaded patients. (PubMed, Br J Haematol) - No abstract available

HEOR • Journal • Real-world evidence • Cardiovascular • Hematological Disorders

Luspatercept initiated at the maximum-approved dose in transfusion-dependent lower-risk myelodysplastic syndromes: Interim analysis from maxilus (ASH 2025) - P3 | "Starting luspatercept at the maximum-approved dose of 1.75 mg/kg was well-tolerated, with no newsafety signals. The high rate of RBC-TI ≥12 weeks in ESA-naive pts suggests that early use of luspaterceptmay contribute to clinical benefit. In this preplanned interim analysis, luspatercept demonstrated efficacyamong pts with LR-MDS, including in those with RS-negative status and baseline sEPO ≤200 IU/L."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • SF3B1

Unpacking the Overlap: Clinical and Molecular Landscape of MDS with del(5q) and SF3B1 (USCAP 2026) - "Treatment patterns differed among the groups, with lenalidomide most commonly used in MDS-5q (64.7%, p<0.01), while luspatercept predominated in MDS-5qSF3B1 (55.6%, p<0.01). MDS-5qSF3B1 demonstrates distinct clinical, morphologic, and molecular features compared to its single-genotype counterparts. These findings support the need for further investigation into the classification and management of this rare dual-genotype MDS subset."

Clinical • Bone Marrow Transplantation • Hematological Malignancies • Myelodysplastic Syndrome • DNMT3A • JAK2 • RUNX1 • SF3B1 • TET2 • TP53 • ZRSR2

THE INFLUENCE OF LUSPATERCEPT ON BONE MARROW MESENCHYMAL STROMAL CELLS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH MYELODYSPLASTIC NEOPLASMS AND ACUTE MYELOID LEUKEMIA (EBMT 2026) - "The obtained in vitro data indicate the ability of luspatercept to enhance the expression of genes responsible for hematopoietic support in bone marrow MSCs of patients with MDS and AML. Further studies are needed to confirm these results and determine the clinical significance of luspatercept use after HSCT."

Clinical • Stroma • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Transplantation • CDH2 • CXCL12 • ITGB1 • VCAM1

THE INFLUENCE OF LUSPATERCEPT ON BONE MARROW MESENCHYMAL STROMAL CELLS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR PATIENTS WITH MYELODYSPLASTIC NEOPLASMS AND ACUTE MYELOID LEUKEMIA (EBMT 2026) - "The obtained in vitro data indicate the ability of luspatercept to enhance the expression of genes responsible for hematopoietic support in bone marrow MSCs of patients with MDS and AML. Further studies are needed to confirm these results and determine the clinical significance of luspatercept use after HSCT."

Clinical • Stroma • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Transplantation • CDH2 • CXCL12 • ITGB1 • VCAM1

A Study of Incidence, Treatment Patterns, and Outcomes in Transfusion-dependent Lower-risk Myelodysplastic Syndromes in Spain (clinicaltrials.gov) - P=N/A | N=1300 | Active, not recruiting | Sponsor: Bristol-Myers Squibb

New trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Clinical Approach to Relapsed or Refractory Lower-Risk Myelodysplastic Syndromes (ICKSH 2026) - "In the phase 3 COMMANDS trial (ESA -naïve TD LR -MDS; IPSS -R very low/low/intermediate; sEPO <500 U/L; <5% blasts; del(5q) excluded), luspatercept significantly improved the primary endpoint (RBC -TI for ≥12 weeks with concurrent mean hemoglobin [Hb] increase ≥1.5 g/dL during weeks 1–24) versus epoetin alfa (60.4% vs 34.8%; p<0.0001). Evidence -based sequencing begins with early ESA use when appropriate, transitions to luspatercept when response is lost, but consider this agent not only in R/R cases, but also as an effective and durable first -line option (with subgroup -consistent benefit), for TD ESA -naïve LR -MDS who do not have probability to respond to ESAs and incorporates imetelstat as a potentially disease -modifying therapy in ESA -failed/ESA -ineligible and lus patercept -failed TD LR - MDS , especially if with high transfusion burden . Molecularly targeted agents and cytogenetically defined approaches (e.g., lenalidomide in del(5q) ,..."

Clinical • Cardiovascular • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia • ACVR2A • IDH1 • IDH2 • SF3B1

Impact of Mutational Landscape and Burden on RBC Transfusion Response in Patients With Lower-Risk Myelodysplastic Syndromes (LR-MDS) in the COMMANDS Study. (PubMed, Am J Hematol) - P3 | "Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Luspatercept represents an effective treatment option in various mutational backgrounds in LR MDS. Trial Registration: ClinicalTrials.gov Identifier: NCT03682536."

Journal • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • SF3B1

The Efficacy and Safety of Luspatercept in Improving Early Anemia After HSCT (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P2 trial • Anemia • Bone Marrow Transplantation • Hematological Disorders • Transplantation

Luspatercept Promotes Hematopoietic Recovery in Patients with Hematological Malignancies: A Series of Five Cases. (PubMed, Indian J Hematol Blood Transfus) - "These 3 cases suggest luspatercept as an effective and safe option for relieving severe anemia caused by hematological malignancies, and thereby relieving the need for blood transfusion. The online version contains supplementary material available at 10.1007/s12288-025-02073-0."

Journal • Hematological Disorders • Hematological Malignancies • Oncology

A Real-World Study to Evaluate Luspatercept in Adults With Transfusion-Dependent Beta-Thalassemia in the Middle East (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2025 ➔ Feb 2026

Enrollment open • Real-world evidence • Trial initiation date • Beta-Thalassemia • Genetic Disorders

How I manage luspatercept in transfusion-dependent beta-thalassemia. (PubMed, Hemasphere) - "In this paper, we present five clinical cases that drive us through the complexity of luspatercept management and highlight the following topics: (1) the role of genotype in the patient selection, (2) the importance of patient empowerment and the psychological aspects when introducing a new therapy, (3) efficacy assessment in the real-world, including improvement of iron balance, optimization of pretransfusion hemoglobin, and (4) the importance of the constant monitoring for safety and for adverse events. Emerging evidence and insights from real-world settings play a crucial role in shaping best practices for everyday clinical practice."

Journal • Beta-Thalassemia • Genetic Disorders • Hematological Disorders

LUSPARA - Luspatercept in patients affected with rare inherited anemias (clinicaltrialsregister.eu) - P1/2 | N=45 | Not yet recruiting | Sponsor: Eurobloodnet Association

New P1/2 trial • Anemia • Hematological Disorders • HSPA9 • RPL11 • RPL5 • RPS26 • SLC25A3

Luspatercept-Associated Intrapulmonary Shunting: A Novel Cause of Unexplained Hypoxemia in a Patient With Myelodysplastic Syndrome (ATS 2026) - No abstract available

Clinical • Hematological Malignancies • Myelodysplastic Syndrome

Bristol Myers Squibb Announces Positive Top-Line Results from Registrational Phase 2 Study of Luspatercept in Adults with Alpha (α)-Thalassemia (Businesswire) - "The non‑transfusion‑dependent (NTD) and transfusion‑dependent (TD) cohorts of the study met their respective primary endpoints, with Reblozyl demonstrating a statistically significant and clinically meaningful increase in hemoglobin levels in NTD patients with α‑thalassemia, and a statistically significant and clinically meaningful decrease in red blood cell (RBC) transfusion burden in TD patients with α‑thalassemia. The study also met all key secondary endpoints. Safety findings were consistent with the known profile of Reblozyl in thalassemia....The data will be presented at an upcoming medical congress and will be discussed with the Center for Drug Evaluation in China."

P2 data • Hematological Disorders

A Study to Evaluate Luspatercept Treatment Patterns and Outcomes in Erythropoiesis-Stimulating Agents-Naïve Patients With Lower-Risk Myelodysplastic Syndromes in the United States (clinicaltrials.gov) - P=N/A | N=418 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Mar 2025

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

TGFβ-Mediated Overexpression of Podoplanin Serves as a Potential Diagnostic Biomarker in Acute Promyelocytic Leukemia. (PubMed, Mol Carcinog) - "Early diagnosis of acute promyelocytic leukemia (APL), driven by PML-RARA oncoprotein, is vital for survival, as delays can cause fatal coagulopathy without prompt therapeutic intervention of all-trans retinoic acid and arsenic trioxide...Pharmacological inhibition of TGF-β1 ligand using luspatercept reduced SMAD phosphorylation and PDPN expression, indicating TGF-β/SMAD transcriptionally regulates PDPN. Additionally, ELISA-based serum profiling showed significantly elevated TGF-β1 levels in APL patients compared to non-APL AML (p < 0.0001). These findings identify PDPN overexpression as a downstream consequence of TGF-β/SMAD signaling and highlight its potential as a diagnostic biomarker for APL."

Biomarker • Journal • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombosis • PDPN • PML • TGFB1

The development of intrapulmonary shunting caused by luspatercept in low grade myelodysplastic syndrome: a case report. (PubMed, AME Case Rep) - "In this report, the complex mechanism of luspatercept is discussed with a literature review on the clinical trials leading to its approval in MDS patients. Furthermore, we connect the pathophysiology between the formation of this patient's telangiectasias leading to her PAVM with the disruption of the TGF-β/SMAD pathway from luspatercept use."

Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Oncology • TGFB1

Mesangial sclerosing glomerulopathy following luspatercept treatment - a case report. (PubMed, BMC Nephrol) - "Clinicians should be aware of possible renal involvement during luspatercept treatment and consider systematic monitoring of kidney function and urinalysis in treated patients. Further data are needed to clarify the spectrum and mechanisms of renal adverse events associated with this drug."

Journal • Acute Kidney Injury • Beta-Thalassemia • Genetic Disorders • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Nephrology • Oncology • Renal Disease • TGFB1

[VIRTUAL] The Commands Trial: A Phase 3 Study of the Efficacy and Safety of Luspatercept Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low-, Low-, or Intermediate-Risk MDS in Erythropoiesis Stimulating Agent-Naive Patients Who Require RBC Transfusions (ASH 2020) - P3 | "Recent studies of epoetin alfa and darbepoetin alfa have demonstrated efficacy among patients with LR-MDS, but the patient population in whom a clinically significant effect is seen may be limited (Fenaux P, et al...Exclusion criteria include prior use of ESAs (≤ 2 doses of prior epoetin alfa permitted if ≥ 8 weeks from randomization date and sEPO confirmed as ≤ 500 U/L), granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), unless given for the treatment of febrile neutropenia; disease-modifying agents (e.g. lenalidomide), or hypomethylating agents; and presence of del(5q) cytogenetic abnormality...Key secondary endpoints include duration of RBC-TI, change in Hb levels, achievement of HI-E response per International Working Group (IWG) 2006 criteria, and safety. The COMMANDS trial is registered at ClinicalTrials.gov (NCT03682536) and EudraCT (number 2017-003190-34)."

Clinical • P3 data • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • CSF2 • EPO • SF3B1

LUSPATERCEPT VERSUS EPOETIN ALFA FOR TREATMENT (TX) OF ANEMIA IN ESA-NAIVE LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS) PATIENTS (PTS) REQUIRING RBC TRANSFUSIONS: DATA FROM THE PHASE 3 COMMANDS STUDY (EHA 2023) - P3 | "Luspatercept demonstrated superiority over epoetin alfa with clinically meaningful improvements in RBC-TIand HI-E rates in ESA-naiveLR-MDS pts who requiretransfusions.Luspatercept showed morefavorable outcomes compared to epoetin alfa across a spectrum of known MDS mutations.Luspatercept safety profile was comparable with previous reports; no new safety events wereidentified.Luspatercept may transform thecurrent landscape by establishing a new standard of tx for ESA-naive pts with transfusion dependent LR-MDS. Keywords: Mutation analysis, Myelodysplastic syndrome,Erythropoieisis, Clinical trial"

Clinical • P3 data • Tumor mutational burden • Acute Myelogenous Leukemia • Anemia • Cardiovascular • Fatigue • Hematological Disorders • Hematological Malignancies • Hypertension • Myelodysplastic Syndrome • Oncology • ASXL1 • DNMT3A • IDH2 • SF3B1 • TET2 • TMB • U2AF1