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

The 'αO2-PRBCThal' trial on the use of hemanext One® for blood transfusion support transfusion-dependent thalassemia (ASH 2025) - P | "The exclusion criteria included (i) a history of any significant medical condition, laboratory abnormality, or psychiatric illness; (ii) a positive Coombs (antiglobulin) test within 6 months prior to enrollment; (iii) planned or recent splenectomy (within 6 months prior to enrollment); (iv) use of luspatercept within 6 months prior to enrollment or at any time during the study; and (v) participation in an interventional clinical trial or use of investigational medications within 6 months prior to enrollment or during the study period.The study aims to assess changes in the transfusion burden, the degree of hemolysis and the presence of metabolic disturbances... Overall, hypoxic storage seems to offer advantages in mitigating oxidative stress, without promoting RBC lysis. The 'αO2-PRBCThal' trial may provide evidence that the HEMANEXT ONE RBC storage method is both safe and able to provide transfusion support to TDT patients without increasing the transfusion..."

Genetic Disorders • Hematological Disorders • Mental Retardation • Metabolic Disorders

Real-world characteristics and treatment patterns of patients with myelodysplastic syndromes treated with luspatercept in Puerto Rico (ASH 2025) - "To our knowledge, these retrospective claims data provide the first insight into patient characteristics and patterns of use for luspatercept in Puerto Rico. Future studies will aim to understand treatment outcomes and health care resource utilization among patients with MDS treated with luspatercept in Puerto Rico. Ultimately, understanding the real-world use of luspatercept may help optimize therapeutic interventions to improve patient outcomes."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Myelodysplastic Syndrome

Evaluation of psychosocial impact of myelodysplastic syndromes evaluation by self report (ASH 2025) - P | "Eight (29.6%) were currently on treatment including DNMTi, erythropoietin, venetoclax, and luspatercept. These data also provide valuable feedback on participation in clinical trials and a host of unmet needs in health care delivery. This information can help health care professionals offer tailored support and planning of future intervention trials to improve clinical outcomes, as well as to help patients cope more effectively with their condition."

Acute Myelogenous Leukemia • CNS Disorders • Depression • Erectile Dysfunction • Hematological Malignancies • Infectious Disease • Mood Disorders • Myelodysplastic Syndrome • Post-traumatic Stress Disorder

Outcomes with luspatercept in patients with β-thalassemia: A systematic review and meta-analysis (ASH 2025) - "Conclusion Luspatercept significantly reduces the transfusion burden in patients with β-thalassemia and demonstrates a favourable safety profile. This study supports the use of luspatercept as an effective and well-tolerated therapeutic option for β-thalassemia while highlighting the need for continued research to consolidate these findings."

Retrospective data • Review • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Musculoskeletal Pain

Baseline findings to inform quality improvement opportunities in low-risk Myelodysplastic Syndromes (ASH 2025) - "12.5% were treated with lenalidomide. 17.9% were treated with luspatercept... Baseline data from this multicenter QI initiative reveals variability in key diagnostic and treatment-related processes for low-risk MDS, with gaps noted in molecular testing, ESA workup, and iron overload monitoring. These findings highlight actionable targets for standardizing care and aligning with best practices. While post-intervention outcomes are pending, these results may guide other centers in identifying and addressing similar gaps to advance patient-centered care in low-risk MDS."

Hematological Malignancies • Myelodysplastic Syndrome

The efficacy and safety of luspatercept in patients with low-blasts myelodysplastic neoplasms in real world (ASH 2025) - "The ESA group were received rhEPO ± roxadustat treatments. It need to optimize the treatment of luspatercept in further. Key words : MDS-LB, luspatercept, EPO refractory, anemia, immune state"

Clinical • Real-world • Real-world evidence • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • CRP • IFNG • IL2 • IL6 • SF3B1 • TNFA

Real-world patient characteristics, treatment patterns, and outcomes in patients with myelodysplastic syndromes (ASH 2025) - "Among LR-MDS patients, 30.6% received ESAs as 1 st -line therapy while 24.8% received other treatments such as hypomethylating agents (9.8%), granulocyte-colony stimulating factor (2.4%), and luspatercept (2.6%); 44.5% received no treatment... Among 561 patients with known IPSS-R risk scores, 418 (74.5%) had LR-MDS and 143 (25.5%) had HR-MDS. Median age at diagnosis was 75.4 years and Elixhauser Comorbidity Score (ECS) was 4. Patients were predominantly male (61.6%) and non-Hispanic White (64.9%)."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Nephrology • Renal Disease

Refractory anemia with ring sideroblasts: Epidemiological survival trends and implications in a SEER population-based study (ASH 2025) - "Available chemotherapies include luspatercept, hypomethylating agents like decitabine and azacitidine in more aggressive or refractory disease, and lenalidomide in del(5q) mutation co-ocurrence. Older patients had notably higher all-cause mortality, likely due to comorbidities as well as increased risk for malignant transformation. More notably, chemotherapy, on average, was associated with worse outcomes, likely reflecting patients with more aggressive disease compared to most untreated counterparts. There is no immediately clear explanation for the modest but significant survival advantage female gender provides."

Clinical • Anemia • Hematological Malignancies • Myelodysplastic Syndrome • SF3B1

Luspatercept for the treatment of myelodysplastic syndrome: A retrospective cohort study utilizing trinetx (ASH 2025) - "Secondary outcomes included overall mortality, transition to hypomethylating agent therapy (decitabine or azacitidine), and the need for allogeneic stem cell transplant...The COMMANDS trial further confirmed the superiority of luspatercept over epoetin alfa in ESA-naïve, transfusion-dependent lower-risk MDS, with a higher rate of RBC-TI ≥12 weeks and a concurrent mean hemoglobin increase ≥1.5 g/dL during weeks 1–24 (60% vs. 35%, p<0.0001)...Conclusion Our findings suggest that luspatercept can provide meaningful and durable benefits for a substantial subset of patients and may serve as an important component of therapy in appropriately selected individuals with very low to intermediate-risk MDS. Future studies are necessary to evaluate which patients would most benefit from treatment with luspatercept."

Retrospective data • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • SF3B1 • TGFB1

Clinical features and outcomes of myeloproliferative neoplasm patients with MPL mutations and concurrent JAK2/calr mutations (ASH 2025) - "ET treatments included hydroxyurea and off-label Ropeginterferon alfa-2b. Among those with MF, 7 patients received ruxolitinib, 2 required anemia-related therapies, including darbepoetin alfa and Luspatercept...However, further work is required to investigate this hypothesis. Limited follow-up and the predominance of White populations in our cohort underscore the need for studies involving larger and more diverse populations with extended longitudinal data to better understand the prognostic significance and therapeutic implications of the co-mutations."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Thrombocytosis • ASXL1 • CALR • JAK2 • NOTCH1 • SF3B1 • SH2B3 • SRSF2 • TET2

Clinical outcomes in spliceosome-mutant myelodysplastic neoplasms and Acute Myeloid Leukemia (ASH 2025) - "A total of 97 patients were retrospectively analyzed, of whom 69% were male, with the median age being 76 years, and non-Hispanic White (92%). The median overall survival (OS) in the entire cohort was 29 (18-40) months. Patients harboring the U2AF1 mutation had the shortest median OS of 15 months, while patients harboring the SF3B1 mutations had the longest median OS of 52 months, although these differences were not significant (p = 0.26)."

Clinical • Clinical data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • SF3B1 • SRSF2 • U2AF1 • ZRSR2

Thalidomide in beta-thalassemia – a systematic review and meta-analysis (ASH 2025) - "Curative therapies such as allogeneic hematopoietic stem cell transplant and disease-modifying therapies such as Luspatercept have become standard of care. All AEs were grade 1-2 and did not require drug discontinuation. Our results suggest that in settings where gold standard therapies may be unavailable, thalidomide may be a promising treatment option for patients with beta-thalassemia."

Retrospective data • Review • Beta-Thalassemia • Bone Marrow Transplantation • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Otorhinolaryngology • Vertigo

A paraspinal extramedullary hematopoiesis with cauda equina syndrome in a transfusion-dependent thalassemia patient after treatment with luspatercept: A case report. (ASH 2025) - "Hydroxyurea was trialed but discontinued due to suspected pancytopenia. While luspatercept offers considerable benefits in reducing transfusion burden in patients with TDT, clinicians should remain vigilant for rare but serious complications such as EMH. Our case highlights that non-invasive management strategies, including intensive transfusion regimens and physiotherapy, may restore function and avoid surgical intervention in select patients. Further reporting and data collection are necessary to inform evidence-based guidelines for the optimal management of EMH in this context."

Case report • Clinical • Anesthesia • Back Pain • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Infectious Disease • Musculoskeletal Pain

Efficacy of luspatercept in reducing transfusion burden and its impact on liver iron concentration in beta-thalassemia major: A systematic review and meta-analysis (ASH 2025) - "Nevertheless, these findings should be interpreted with caution, as one of the studies did not include a placebo group, which limits the robustness of the comparison. Further confirmation by additional randomized clinical trials is needed to validate these results and to determine in more detail their role in clinical practice."

Retrospective data • Review • Beta-Thalassemia • Genetic Disorders • Hematological Disorders

Predictive biomarkers of luspatercept and erythropoiesis-stimulating agent (ESA) hematological response and overall survival (OS) in patients with lower-risk myelodysplastic syndromes (LR-MDS) in the commands trial (ASH 2025) - P3 | "In thephase 3 COMMANDS trial (NCT03682536), luspatercept demonstrated superiority for the primaryendpoint (PE) of transfusion independence (TI) vs ESA epoetin alfa, including a trend for improved OS. Key baseline variables including IPSS-M, number of mutations, mutational burden, soluble proteins, andpatient characteristics were balanced between tx arms (luspatercept, n=182; ESA, n=181). Luspaterceptdemonstrated superiority vs ESA for RBC-TI (PE; 60% vs 35%) with a trend for improved OS (median, notestimable vs 46 mo).Univariate analysis identified significant explanatory variables across both tx arms (P<0.05) for the PE(n=35) and OS (n=40). For the luspatercept arm, significant PE predictors were lower IPSS-M anderythropoietin (EPO) levels, and higher alpha-2 macroglobulin (P<0.001)."

Biomarker • Clinical • Tumor mutational burden • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • A2M • ASXL1 • GDF15 • MB • SF3B1 • TMB

Remark: A phase II, open-label, multicenter study of orally administered romaciclib (RVU120) for the treatment of anemia in patients with lower-risk myelodysplastic neoplasms (LR-MDS) (ASH 2025) - P2 | "Hereceived three prior lines of therapy with ESA, luspatercept, and lenalidomide. Despite the preliminary nature of the data, initial signs of clinical activity of romaciclib in patients with LR-MDS were observed. Ongoing analyses in the study aim at describing the clinical and molecular changesduring treatment with romaciclib, at identifying the optimal dose and schedule as well as potentialpredictors of response."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • SF3B1

Luspatercept response predictors in lower-risk myelodysplastic syndrome (ASH 2025) - "There was no significant association with prior ESA or lenalidomide use. Patients who respond to luspatercept tend to have lower baseline transfusion burden, lowerRS%, and no prior HMA therapy. Attainment of response was associated with significantly improvedoverall survival. Prospective studies are needed to validate these predictors and inform optimalsequencing of luspatercept in LR-MDS."

Hematological Malignancies • Immunology • Myelodysplastic Syndrome • ASXL1 • DNMT3A • SF3B1 • SRSF2 • TET2 • TGFB1 • U2AF1

Real-world treatment patterns and outcomes of first-line luspatercept in patients with myelodysplastic syndromes in the United States (ASH 2025) - "In real-world practice, patients with MDS treated with 1L luspatercept achieved TI and mHI-E, withresponse rates comparable to those observed in the registrational clinical trial. Therapeutic benefits with1L luspatercept were observed across all subgroups, including RS- and sEPO <200 U/L populations.Overall, 27.5% of patients required dose escalation and 36.7% discontinued treatment before receivingthe maximum luspatercept dose recommended by its prescribing information, primarily due to lack ofresponse. Additionally, 2L ESA remained an effective treatment following 1L luspatercept discontinuation.These findings highlight the clinical benefit of luspatercept, demonstrating its effectiveness as atreatment option for patients with MDS in real-world clinical practice."

Clinical • HEOR • Real-world • Real-world evidence • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome

Luspatercept for the treatment of transfusion-dependent anemia in patients with myelodysplastic neoplasms with del5q, refractory/resistant/intolerant to prior treatments (QOL-ONE Phoenix) (ASH 2025) - "Lenalidomide is the targetedtreatment for MDS with del5q able to abrogate RBC TD with a median duration of response of 2-3 years.However, about a third of patients are refractory/resistant/ ineligible to lenalidomide and will remain RBCTD. This interim analysis shows that luspatercept is an effective treatment in a substantialproportion of cases with MDS with del5q, with concurrent improvements in Hb levels, while maintaining afavourable safety profile. Additionally, a notable improvement in QoL is reported. Longer follow-up isrequired to confirm the durability of these benefits."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Pneumonia • Respiratory Diseases

Azacitidine and luspatercept metronomic therapy for intermediate- to high-risk myelodysplastic syndrome: A prospective single-center phase II clinical trial (ASH 2025) - "Metronomic therapy with azacitidine combined with luspatercept appears to be an effective and safeapproach for intermediate- to high-risk MDS patients. Patients with myelofibrosis can also benefit fromthis regimen."

Clinical • P2 data • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Musculoskeletal Diseases • Myelodysplastic Syndrome • Myelofibrosis • Neutropenia • Orthopedics • Respiratory Diseases • ASXL1 • DNMT3A • SF3B1 • TET2 • TP53

Not all that glitters is gold: A simple clinical score to unmask adverse SF3B1WT MDS-RS with low blast count (ASH 2025) - "Additionally, in MDS-LB-RScases with IPSS-R ≤ 3.5, erythroid response to erythropoiesis stimulating agents (ESAs) and luspatercept(Luspa) was compared adopting IWG 2018 criteria...Infact, these patients warrant closer monitoring due to their adversegenetic profile and inferior prognosis. Furthermore, their apparent lower response to standard anemiatherapies suggests a need for alternative treatment approaches."

Clinical • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • KIT • SF3B1 • SRSF2 • TP53 • U2AF1

Clinical features and outcomes of myelofibrosis patients with MPL mutations (ASH 2025) - "Treatment regimensincluded JAK inhibitors, most commonly Ruxolitinib (n=31), Momelotinib (n=4), Fedratinib (n=2), andPacritinib (n=1). Anemia-directed therapies included erythropoietin-stimulating agents (ESA) in 21patients, Danazol (n=9), and Luspatercept (n=2)...A significant subset of patients progressed to accelerated-phase disease or AML (n=11, 15%).Despite this, only one-fifth underwent hematopoietic stem cell transplantation. These results highlightedthe need for improved risk stratification and the development of targeted therapeutic strategies for thisrare and understudied population."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • ASXL1 • CALR • JAK2 • SRSF2 • U2AF1

Luspatercept combined with immunosuppressive therapy reduces inflammation in aplastic anemia by inhibiting monocyte pyroptosis (ASH 2025) - "CD8+ T cells were further co-cultured with monocytes to assess their functional activity andcytokine secretion profile. The triple therapy (luspatercept + cyclosporine + eltrombopag) significantly restoredhematopoietic function in patients with SAA. This study demonstrates that luspatercept achieves multi-target immunomodulation inpatients with SAA by inhibiting the NF-κB/NLRP3 crosstalk in monocytes. This action mitigatesinflammation and pyroptosis, disrupting the pathogenic cycle and promoting hematopoietic recovery."

Anemia • Aplastic Anemia • Hematological Disorders • Immunology • Inflammation • CD14 • CD8 • GLI2 • NLRP3

Impact of long-term luspatercept treatment on iron parameters in patients with transfusion-dependent and non-transfusion-dependent β-thalassemia: Results from the phase 3b long-term follow-up study (ASH 2025) - P3 | "These data from the phase 3b LTFU study of luspatercept indicate that long-term treatmentof patients with TDT led to durable reductions in RBC transfusion burden, LIC, and SF levels, while cardiaciron markers remained stable. LIC also decreased in patients with NTDT who received luspatercept withICT and remained stable in patients without ICT, whereas SF remained stable with luspaterceptregardless of ICT status. Overall, these data suggest long-term luspatercept treatment of patients withTDT and NTDT is associated with durable benefit."

Clinical • P3 data • Anemia • Beta-Thalassemia • Genetic Disorders • Hematological Disorders

A phase 2 study of luspatercept in adults and adolescents with α-thalassemia: Findings from the dose-confirmation cohort in adolescents (ASH 2025) - P2 | "In this analysis from the dose-confirmation phase of luspatercept in adolescent patientswith TD and NTD α-thalassemia HbH disease, no DLTs or new safety signals were reported, suggestingthat the RD of 1.0 mg/kg is well-tolerated in these patients. Enrollment in the TD and NTD dose-expansion cohorts is ongoing."

Clinical • P2 data • Anemia • Beta-Thalassemia • Cardiovascular • Genetic Disorders • Infectious Disease • Musculoskeletal Diseases • Orthopedics • Respiratory Diseases