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

Luspatercept-Induced Hyperammonemia and Hepatic Encephalopathy in a Cirrhotic Patient (ACG 2026) - "He had MDS treated with Luspatercept infusions every 3 weeks and was maintained on lactulose 45 g TID and rifaximin 550 mg BID. Luspatercept may provoke hyperammonemia and HE in cirrhotic patients with limited ammonia clearance capacity. Clinicians should exercise caution when administering high-protein biologics in patients with TIPS or recurrent HE and consider individualized preventive strategies."

Clinical • Cardiovascular • CNS Disorders • Cognitive Disorders • Fibrosis • Hematological Malignancies • Hepatic Encephalopathy • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Myelodysplastic Syndrome • Portal Hypertension

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

Results from a Phase 1 Open-Label Dose Escalation and Expansion Trial of Oral Azacitidine + Cedazuridine (ASTX030) in Patients with Myelodysplastic Syndromes (MDS) and MDS/Myeloproliferative Neoplasms (MPN) (ASH 2024) - P2/3 | "Background : Azacitidine (AZA) and decitabine (DEC) are parenteral DNA methyltransferase inhibitors (DNMTis) approved for the treatment of patients with MDS and acute myeloid leukemia...Median age was 72 years (range, 26–87), 35% (n=31) of patients were female, prior treatments included DNMTis (9% [n=8]), luspatercept (3% [n=3]), lenalidomide (3% [n=3]), and erythropoiesis‑stimulating agents (3% [n=2])...Based on the results of the phase 1 trial, 140/20 mg AZA/CED was selected as the RP2D. Enrollment for the phase 2 randomized, crossover (oral vs SC) trial is ongoing and combination dosing is in preparation."

Clinical • P1 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

Real-World Outcomes of Imetelstat: Interrogating Safety, Efficacy, and Predictors of Response in Heavily Pretreated Lower-Risk Patients With MDS (SOHO 2026) - "Imetelstat was used as later line of therapy (median, third line); 35 patients (87.5%) had prior luspatercept, 28 patients (70%) had prior ESA, 15 patients (37.5%) had prior HMA, and 17 patients (42.5%) had prior lenalidomide. Real-world experience confirms safety and clinical efficacy of imetelstat in LR-MDS, including patients with extensive prior therapies and luspatercept failure. We report novel predictors of response, including baseline platelet count and ASXL1 mutation. ASXL1: ASXL transcriptional regulator 1, AUC: area under the curve, EPO: erythropoietin, ESA: erythropoiesis-stimulating agent, G-CSF: granulocyte-colony stimulating factor, Hb: hemoglobin, HMA: hypomethylating agent, IPSS-M: International Prognostic Scoring System-Molecular, IPSS-R: International Prognostic Scoring System-Revised, MDS: myelodysplastic syndromes, OR: odds ratio, OS: overall survival, RBC: red blood cell, RBC-TI: red blood cell–transfusion independence, SF3B1: splicing factor 3b..."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ASXL1 • SF3B1 • TET2

Longitudinal Safety of Luspatercept in the Treatment of Anemia in Patients with Myelofibrosis: Results from the ACE-536-MF-001 Study (ASH 2023) - P2 | "Methods Pts were enrolled into 4 cohorts based on transfusion dependence (TD) and stable ruxolitinib (RUX) treatment – cohort 1: NTD, no RUX; cohort 2: TD, no RUX; cohort 3A: NTD, RUX; cohort 3B: TD, RUX...Results In the safety population (N = 95; cohort 1, n = 22; cohort 2, n = 14; cohort 3A, n = 21; cohort 3B, n = 38), the most frequently used prior medications for anemia treatment were erythropoiesis-stimulating agents (23.2%, most frequently epoetin alfa [14.7%]), followed by danazol (11.6%), lenalidomide (2.1%), and thalidomide (1.1%)...In addition to benefits in anemia, the safety profile of LUSPA allowed most pts receiving RUX to maintain or increase their RUX dose, supporting maintenance of Janus kinase inhibitor therapy for adequate disease control of MF. Study support: Bristol Myers Squibb."

Clinical • Anemia • Beta-Thalassemia • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Inflammation • Ischemic stroke • Musculoskeletal Pain • Myelodysplastic Syndrome • Myelofibrosis • Oncology • Pain • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock

Preliminary safety and efficacy of oral azacitidine (Oral-AZA) in patients (pts) with low-/Intermediate (Int)-risk myelodysplastic syndromes (MDS): Phase 2 results from the ASTREON trial. (ASCO 2024) - P2/3 | "Most pts (42/47 [89.4%]) had prior MDS tx, including but not limited to erythropoiesis-stimulating agents, lenalidomide, luspatercept, and imetelstat. The safety of Oral-AZA 200 mg and 300 mg was consistent with the known Oral-AZA safety profile. Preliminary efficacy data support continued evaluation of Oral-AZA in LR-MDS."

Clinical • P2 data • Acute Myelogenous Leukemia • Anemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

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) | Initiation date: Sep 2026 ➔ Dec 2026

Trial initiation date • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

EFFICACY AND SAFETY OF LUSPATERCEPT IN PATIENTS WITH MYELOFIBROSIS ON JANUS KINASE INHIBITORS WHO REQUIRE RED BLOOD CELL TRANSFUSIONS: PRIMARY ANALYSIS OF THE PHASE 3 INDEPENDENCE TRIAL (EHA 2026) - P2, P3 | "Luspatercept (LUSPA), a first-in-class erythroid maturation agent, demonstrated improvement in Hb levels and reduction in RBCT burden in the phase 2 ACE-536-MF-001 trial in pts with MF (NCT03194542), as a single agent or with ruxolitinib. The LUSPA safety profile was manageable and similar to that expected in advanced MF. Consistent with phase 2 results, these findings suggest LUSPA may offer a potential treatment option for pts with MF-associated anemia who have limited therapeutic options."

Clinical • P3 data • Hematological Disorders • Myelofibrosis

Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes (ASH 2024) - P2/3 | "Prior lenalidomide (LEN) and prior hypomethylating agent (HMA) use were exclusion criteria in phase 3 only. In this analysis, IME-treated patients (N=226) were pooled from phase 2, phase 3, and the QTc study of IMerge and analyzed on the basis of prior treatment as follows : ± ESA, luspatercept (LUSP), LEN, and HMA...Conclusions : Patients who were ESA-ineligible or who had prior treatment with LUSP, LEN, or HMA in IMerge experienced clinical benefit from IME treatment, though the number of patients was small. Given the evolving therapeutic landscape for LR-MDS and the limited data available on outcomes in later lines of treatment, these results have important clinical implications, suggesting that IME demonstrates clinical activity regardless of prior therapies."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

[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

Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis: Results from the ACE-536-MF-001 study. (ASCO 2023) - P2 | " Eligible pts comprised 4 cohorts based on transfusion dependence (TD, defined as receiving 4–12 red blood cell [RBC] units/84 days [d] immediately up to cycle 1 d 1) and stable ruxolitinib (RUX) treatment; cohort 1: no TD, no RUX; cohort 2: TD, no RUX; cohort 3A: no TD, RUX; cohort 3B: TD, RUX. In pts with MF, the safety profile of LUSPA was consistent with previous studies and efficacy results showed promising improvements in anemia and transfusion burden in all cohorts. Clinical trial information: NCT03194542."

Clinical • Acute Myelogenous Leukemia • Anemia • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hypertension • Infectious Disease • Ischemic stroke • Leukemia • Myelofibrosis • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock

A Multicenter, Phase Ib/II Study That Combines Luspatercept and Lenalidomide (L2) in Lower-Risk, Non-Del(5q) Patients with Myelodysplastic Syndromes: Phase Ib Results (ASH 2024) - "Conclusions : The combination of Len + Lusp (L2) was well-tolerated, and a recommended phase II dose was established, with that trial ongoing. The preliminary response rate appeared at least similar to either monotherapy."

Clinical • P1/2 data • Anemia • Fatigue • Gastrointestinal Disorder • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • ASXL1 • CALR • CSNK1A1 • DNMT3A • IDH2 • JAK2 • NRAS • SF3B1 • TET2 • U2AF1

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) | Initiation date: Jun 2026 ➔ Sep 2026

Trial initiation date • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Combining ESA and Luspatercept in Non-RS MDS Patients Having Failed ESA - Results of the Phase 1-2 Part a of the GFM Combola Study (ASH 2024) - "Based on a TITE-BOIN-ET design, Epoetin alfa was administered weekly at dose concentrations ranging from 30 000UI to 60 000 UI...All patients had resistance to ESA and 7 had also received Revlimid (n=3), IDH inhibitors (n=2), Thalidomide (n=1), AZA (n=1)...Based on the results of this Phase 1 study, the dosing schedule Luspatercept 1.75 mg/kg/21d and EPO 60 000 UI/w, that balanced clinical efficacy and safety profile was selected as the RP2D. This regimen is being compared to Luspatercept 1.75 mg/kg/21d in the ongoing randomized Phase 2 study."

Clinical • P1/2 data • Anemia • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Myelodysplastic Syndrome

LUSPAMARK: Plasmatic Biomarkers Associated With Short-term Luspatercept Treatment of Lower Risk Myelodysplastic Syndromes (MDS) Patients (clinicaltrials.gov) - P4 | N=150 | Not yet recruiting | Sponsor: University Hospital, Grenoble

Biomarker • New P4 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Myelodysplastic Syndrome With SF3B1 Mutation Hidden Behind Anemia of Chronic Kidney Disease: A Diagnostic Odyssey in a Transfusion-Dependent Patient (SOHO 2026) - "Timely molecular characterization is essential to connect patients with disease-modifying therapies when you consider that luspatercept achieved 59% transfusion independence in the COMMANDS trial (vs 31% epoetin alfa), imetelstat demonstrated clonal burden reduction in the IMerge trial, and IPSSM enables precision risk stratification. This case advocates for incorporating bone marrow biopsy with next-generation sequencing into the diagnostic algorithm for ESRD patients with unexplained transfusion dependence in the era of precision hematology. CABG/PCI: coronary artery bypass grafting/percutaneous coronary intervention, CAD: coronary artery disease, COPD: chronic obstructive pulmonary disease, DNMT3A: DNA methyltransferase 3 alpha, ESRD: end-stage renal disease, FFP: fresh frozen plasma, GI: gastrointestinal, HFmrEF: heart failure with mildly reduced ejection fraction, IPSS-M: International Prognostic Scoring System-Molecular, IWG-PM: International Working Group for..."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • DNMT3A • PPM1D • SF3B1

LUSPATERCEPT (LUSPA) INITIATED AT THE MAXIMUM-APPROVED DOSE IN PATIENTS (PTS) WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS) WHO REQUIRE TRANSFUSIONS: PRIMARY ANALYSIS FROM MAXILUS (EHA 2026) - P3 | "LUSPA was well tolerated; few pts progressed to HR-MDS, in line with known rates, and none to AML. The MAXILUS primary analysis reinforces the favorable safety and efficacy profile of LUSPA at the maximum-approved dose in LR ‑ MDS."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • SF3B1

A Study to Determine the Efficacy and Safety of Luspatercept in Adult Participants and to Evaluate the Safety and Pharmacokinetics in and Adolescent Participants With Alpha (α)-Thalassemia (clinicaltrials.gov) - P2 | N=189 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Genetic Disorders • Hematological Disorders

Overall Survival and Progression-Free Survival of Patients Following Luspatercept Treatment in the MEDALIST Trial (ASH 2022) - "Although the MEDALIST trial was not specifically powered to assess OS or PFS, these data show that achieving response with luspatercept treatment increased OS probability. Luspatercept was associated with increased 36-mo OS probability for pts with IPSS-R Very low-risk MDS and 36-mo PFS probability in pts with a BL serum EPO level of 100 to ≤ 200 U/L. Therefore, pts with LR-MDS with these BL characteristics may derive greater survival benefit from luspatercept."

Clinical • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Oncology

Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study. (PubMed, J Clin Oncol) - "Lower baseline erythropoietin levels in non-RS patients (69.6 v 623.3 IU/L; P = .0077) and higher late to early erythroid progenitor cell ratio (10.44 v 4.48; P = .0106) in RS patients were associated with HI-E. This study highlights luspatercept's effects across LR-MDS subtypes, including untreated MDS-RS, serving as a platform for future trials."

Journal • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study. (PubMed, Ann Hematol) - P3 | "These data have implications for clinical practice, as transfusion units and visits are less in luspatercept-treated patients through week 25 regardless of baseline transfusion burden, and continuing luspatercept beyond week 25 can potentially provide additional clinical benefits for initial nonresponders. Trial registration: NCT02631070."

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

Efficacy and safety results from the COMMANDS trial: A phase 3 study evaluating luspatercept vs epoetin alfa in erythropoiesis-stimulating agent (ESA)‑naive transfusion-dependent (TD) patients (pts) with lower‑risk myelodysplastic syndromes (LR-MDS). (ASCO 2023) - P3 | "Compared with epoetin alfa, luspatercept led to clinically meaningful and statistically significant improvements in RBC-TI and erythroid response, as well as duration of response. Luspatercept safety results were consistent with previous findings. These data show, for the first time, superiority of an innovative therapy over ESAs in ESA-naive pts with TD LR-MDS."

Clinical • P3 data • Acute Myelogenous Leukemia • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

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

Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. (PubMed, Lancet) - P3 | "In this interim analysis, luspatercept improved the rate at which red blood cell transfusion independence and increased haemoglobin were achieved compared with epoetin alfa in ESA-naive patients with lower-risk myelodysplastic syndromes. Long-term follow-up and additional data will be needed to confirm these results and further refine findings in other subgroups of patients with lower-risk myelodysplastic syndromes, including non-mutated SF3B1 or ring sideroblast-negative subgroups."

Journal • P3 data • P3 data: top line • Acute Myelogenous Leukemia • Cardiovascular • Fatigue • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Novel Coronavirus Disease • Oncology • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • SF3B1

Luspatercept Versus Epoetin Alfa (EA) for Treatment of Anemia in Patients With Erythropoiesis‑Stimulating Agent (ESA)‑Naive Lower‑Risk Myelodysplastic Syndromes (LR‑MDS) Requiring Red Blood Cell (RBC) Transfusions: Data from the Phase III COMMANDS Study (SOHO 2023) - P3 | "Almost twice as many patients achieved RBC-TI and hemoglobin increase with luspatercept versus EA; luspatercept delivered more durable responses and clinical benefit regardless of subgroups, with a manageable safety profile and no new safety signals. Luspatercept is the first therapy demonstrating superiority against ESAs."

Clinical • P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology