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

Luspatercept for Patients with Lower-Risk Myelodysplastic Syndromes/Neoplasms: A Systematic Review and Meta-Analysis. (PubMed, Blood Adv) - "Luspatercept is an effective and well-tolerated treatment for anemia in TD LR-MDS, especially in RS⁺ and LTB patients. Its favorable safety profile and higher TI rates, particularly in ESA-naïve populations supports its use in the frontline setting."

Journal • Retrospective data • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Real-World Outcomes and Predictors of Response and Progression in Lower-Risk Myelodysplastic Syndrome Patients Treated With Luspatercept: A Single-Center Experience (SOHO 2025) - "Subsequent therapies included best supportive care (n = 14), HMA ± venetoclax (n = 3), danazol (n = 2), and investigational agents (n = 2). Luspatercept showed favorable efficacy in LR-MDS in a real-world setting. Baseline RBC-TB emerged as a reliable predictor of response. However, predictors of progression remain undefined."

Clinical • Real-world • Real-world evidence • Tumor mutational burden • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • SF3B1 • TMB

Individualizing Treatment Selection in MF (SOHO 2025) - P3 | "These include the activin receptor ligand trap luspatercept, the telomerase inhibitor imetelstat, the selective inhibitor of nuclear export selinexor, the human double minute 2 inhibitor navtemadlin, and the bromodomain and extra-terminal protein inhibitor pelabresib...Elritercept — another activin receptor ligand trap — and the anti-hemojuvelin antibody DISC-0974 are being developed for anemia of MF...Currently, these patients are observed or managed for thrombotic risk similarly to those with essential thrombocythemia (ET) — receiving hydroxyurea for control of cytoses, ruxolitinib for symptoms, or interferon for long-term disease modification. Encouraging data on ruxolitinib in patients with intermediate-1-risk MF, along with analyses from the COMFORT trials demonstrating the benefits of early initiation of ruxolitinib in patients with intermediate-2/high-risk MF and intriguing evidence of event-free survival (EFS) improvement with both ruxolitinib and..."

Clinical • Essential Thrombocythemia • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Non-melanoma Skin Cancer • Oncology • Polycythemia Vera • Skin Cancer • Solid Tumor • ACVR1 • IRAK1

Luspatercept Treatment in a β-Thalassemia Patient with Pulmonary Arterial Hypertension: A Case Report. (PubMed, Mediterr J Hematol Infect Dis) - No abstract available

Journal • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Efficacy and Safety in Transfusion Independent Non-severe Aplastic Anemia (clinicaltrials.gov) - P2 | N=58 | Completed | Sponsor: Bing Han | Not yet recruiting ➔ Completed | N=90 ➔ 58 | Trial completion date: Jul 2024 ➔ Apr 2025 | Trial primary completion date: Jan 2023 ➔ Feb 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Anemia • Aplastic Anemia • Hematological Disorders

Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation. (PubMed, Hereditas) - "These findings suggest that Tln1 and TGFβ2 may play important roles in HF development through the regulation of anoikis and may serve as therapeutic targets for HF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • TGFB1 • TGFB2 • TLN1

Beyond Hypomethylating Agents: Novel Therapies and Targeted Approaches. (PubMed, Clin Hematol Int) - "While early excitement was significant, clinical trials of the immune checkpoint inhibitors (ICIs) ipilimumab and durvalumab have produced no definitive results, highlighting the need for better patient selection and combination regimens. Emerging drugs luspatercept and imetelstat have been suggested for lower-risk MDS (LR-MDS) by promoting transfusion independence and global hematologic response. In contrast, exploratory agents such as pevonedistat, magrolimab, and sabatolimab are under further investigation for HR-MDS...Identification of predictive biomarkers for response to targeted therapies and immunotherapies is crucial to optimize patient outcomes. An integrated, patient-centered approach combining genomics, novel therapeutics, and immunomodulation is therefore essential to address the current needs in MDS management."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology

The 511th case: severe anemia with increased ringed sideroblasts (PubMed, Zhonghua Nei Ke Za Zhi) - "While luspatercept demonstrated short-term efficacy in this patient with non-clonal SA, caution is warranted regarding potential masking of the underlying etiology. Concurrent monitoring of iron overload and early initiation of iron chelation therapy are crucial in alcoholic SA to prevent hepatic damage."

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

Treatment patterns and outcomes in patients with lower-risk myelodysplastic syndromes treated with erythropoiesis-stimulating agents in a large US community oncology practice: a retrospective chart review. (PubMed, J Med Econ) - "Patients treated with luspatercept prior to ESAs or enrolled in clinical trials during the study period were excluded...In this real-world evaluation of ESA treatment in a population with LR-MDS, only one-third of patients experienced hematologic improvement and two-thirds of patients remained on ESA treatment for ≥1 year after failure. These results demonstrate high rates of ESA failure and indicate patients in community oncology settings in the US may be continuing with ESA treatment despite failure."

Journal • Retrospective data • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Treatment for VEXAS syndrome with luspatercept combined with cyclosporine A, methylprednisolone, and thalidomide: a case report (PubMed, Zhonghua Xue Ye Xue Za Zhi) - No abstract available

Journal

Luspatercept combined with roxadustat in the treatment of refractory myelodysplastic neoplasms with ring sideroblasts: a prospective, randomized, single-center study (PubMed, Zhonghua Xue Ye Xue Za Zhi) - " Luspatercept combined with roxadustat shows comparable efficacy and safety to luspatercept monotherapy in the treatment of refractory low-risk MDS-RS. Clinical trial register: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing (K3697)."

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

Outcomes of Imetelstat Therapy in Patients With Ring Sideroblast-Negative (RS-) Lower-Risk Myelodysplastic Syndromes (LR-MDS) From the Pooled IMerge Study Populations (SOHO 2025) - P2/3 | "Baseline characteristics were similar to the phase 3 population: median baseline transfusion burden of 6.5 U/8 weeks, median of 2.8 years from initial diagnosis, 51% with serum erythropoietin ≤500 mU/mL, and 79% and 6% with prior ESA and luspatercept treatment, respectively. Results from this post hoc analysis align with prior findings and support the use of imetelstat in patients with ESA R/R/ ineligible, RS- LR-MDS for whom there are currently no FDA-approved therapies. Funding: Geron Corporation."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Advances and Challenges in the Management of Myelodysplastic Syndromes. (PubMed, Cancers (Basel)) - "For lower-risk MDS, the treatment paradigm has evolved beyond erythropoiesis-stimulating agents (ESAs) with the introduction of novel effective agents such as luspatercept and imetelstat, as well as shortened schedules of hypomethylating agents (HMAs). This review provides a comprehensive overview of the current treatment approach for MDS, highlighting new classifications, prognostic tools, evolving therapeutic options, and ongoing challenges. We discuss evidence-based recommendations, treatment sequencing, and emerging clinical trials, with a focus on translating biological insights into improved outcomes for patients with MDS."

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

Survival Benefit and Resource Utilization of First-Line Treatment With Luspatercept vs First-Line Erythropoiesis-Stimulating Agents for Lower-Risk Myelodysplastic Syndromes: Results of Model Simulation (SOHO 2025) - P2/3, P3 | "First-line (1L) treatments for anemia include luspatercept and erythropoiesis-stimulating agents (ESAs); second-line (2L) treatments include luspatercept, imetelstat, ESAs, and best supportive care (BSC). This analysis indicates that 1L luspatercept treatment is associated with longer patient survival, gain in QALYs, and lower transfusion and HCRU burden compared with 1L ESA, regardless of 2L treatment choice."

Clinical • HEOR • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Efficacy and safety of luspatercept in non-transfusion-dependent β-thalassemia: long-term results from the BEYOND study. (PubMed, Blood Adv) - P2 | "Luspatercept is a valuable treatment option for patients with NTDT, addressing the need for effective long-term treatment of anemia. NCT03342404."

Clinical • Journal • Back Pain • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Hematological Disorders • Musculoskeletal Pain • Pain

Overall Survival (OS) and Duration of Red Blood Cell-Transfusion Independence (RBC-TI) for First-Line Erythropoiesis-Stimulating Agent (ESA)-Naive Patients With Lower-Risk Myelodysplastic Syndromes (LR-MDS) Treated With Luspatercept (LUSPA) vs Epoetin Alfa (EA) in the COMMANDS Trial (SOHO 2025) - P3 | "LUSPA improved duration of response versus EA, with a positive OS trend overall and across subgroups, with no new safety concerns. Longer follow-up is required to confirm these data. These data support LUSPA as treatment for anemia in first-line LR-MDS."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Real-World Treatment Patterns and Outcomes of Luspatercept in Treatment-Naïve Patients With Lower-Risk Myelodysplastic Syndromes (LR-MDS) in a Large US Community Oncology Practice (SOHO 2025) - "As of February 2025, 52 patients met inclusion criteria. Median age at diagnosis was 79.0 years, 65% were male, and 92% were White patients. Moreover, 46% of patients had ring sideroblasts (RS) <5%, 25% had RS ≥15%, 31% had serum erythropoietin <200 U/L, and mean hemoglobin (Hb) level of 9.2 g/ dL prior to treatment."

Clinical • HEOR • Real-world • Real-world evidence • Tumor mutational burden • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • TMB

Transfusion-Dependent MDS With Ring Sideroblasts and Incidental Low-Grade Lymphoma: A Complex Hematologic Intersection (SOHO 2025) - "Therapy with luspatercept was started, and despite escalating dose to 1.75 mg/m2, he has remained transfusion-dependent (1-2 units/week)... MDS with incidental lymphoma requires comprehensive evaluation to guide therapy. Molecular profiling is critical for accurate diagnosis, and transfusion-dependent cases may benefit from early consideration of advanced treatments. Long-term monitoring is essential to assess disease progression."

Hematological Malignancies • Indolent Lymphoma • Lymphoma • Myelodysplastic Syndrome • Oncology • Pancreatic Cancer • Solid Tumor • SF3B1 • TET2

Preliminary Efficacy and Safety Analysis of the MAXILUS Study of Luspatercept (LUSPA) Initiated at the Maximum Approved Dose in Transfusion-Dependent (TD) Lower-Risk Myelodysplastic Syndromes (LR-MDS) (SOHO 2025) - P3 | "LUSPA initiated at the maximum approved dose was well-tolerated with low discontinuation rates and exhibited promising efficacy. Preliminary data indicate that starting LUSPA at this dose may help patients with frontline and previously treated MDS achieve optimal responses. This abstract was accepted and previously presented at the European Hematology Association 2025 Congress."

Clinical • 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 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed

HEOR • Real-world evidence • Trial completion • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

A prospective, single-center, single-arm phase II clinical study of luspatercept combined with azacitidine in the treatment of intermediate-and high-risk myelodysplastic syndromes (ChiCTR) - P2 | N=40 | Recruiting | Sponsor: West China Hospital, Sichuan University; West China Hospital, Sichuan University

New P2 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Novel treatment strategies for lower-risk myelodysplastic neoplasms (PubMed, Rinsho Ketsueki) - "Since anemia is the main symptom of this disease, red blood cell transfusions, darbepoetin, anabolic steroids, and immunosuppressive agents are considered when the disease is symptomatic, but with the advent of the novel anti-anemic agent luspatercept, there is growing debate regarding the timing of therapeutic intervention and the hemoglobin (Hb) levels at which red blood cell transfusion should be considered in this disease...It has become clear that there are slight differences in the criteria for initiation of transfusion and the timing of therapeutic intervention with anti-anemic agents at different centers. In this review, we will discuss the extent to which therapeutic intervention for lower-risk MDS improves the quality of life (QOL) of patients and how to improve the efficiency of limited healthcare resources, including an overview of ongoing clinical trials."

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

Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms (clinicaltrials.gov) - P2 | N=70 | Suspended | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Sep 2025 ➔ Sep 2026 | Recruiting ➔ Suspended | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Trial suspension • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • SF3B1

Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients (clinicaltrials.gov) - P1/2 | N=50 | Suspended | Sponsor: Mikkael Sekeres, MD | Recruiting ➔ Suspended

Trial suspension • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Management of Anemia in Lower-Risk Myelodysplastic Syndromes/Neoplasms With Novel Agents. (PubMed, JCO Oncol Pract) - "Novel insights in the pathogenesis of MDS and results from positive phase III clinical trials in LR-MDS have led to a growing number of therapeutic options (eg, luspatercept and imetelstat). Imetelstat was recently added as a new agent for patients who are refractory/resistant or ineligible for erythropoiesis-stimulating agent treatment on the basis of the randomized phase III IMerge trial, showing that imetelstat led to the primary end point of RBC-TI for ≥8 weeks in 40% of patients compared with 15% in patients receiving placebo. However, future clinical trials are needed to investigate the optimal sequencing of different agents and the potential of improving efficacy using combination of therapeutic strategies in LR-MDS."

Journal • Review • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology