{ "abstract": "Background: MAXILUS is an open-label, global, phase 3b study (NCT06045689) evaluating luspatercept (LUSPA) initiated at the maximum-approved dose (1.75 mg/kg) in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) who are erythropoiesis-stimulating agent (ESA)–naive or –relapsed/refractory or intolerant (R/R/I) and require transfusions. Aim: To report safety and efficacy outcomes of LUSPA based on primary analysis of MAXILUS after 24 wks of treatment (tx). Material and Methods: Eligible pts (≥ 18 y; non-del[5q] LR-MDS per IPSS-R; ≥ 1 unit packed red blood cells [RBCs] ≤ 8 wks before tx; ECOG PS ≤ 2) received SC LUSPA 1.75 mg/kg Q3W. Primary endpoint (PE) was RBC-transfusion independence (RBC-TI) ≥ 8 wks with concurrent mean Hb increase ≥ 1 g/dL (Wks 1–24). Secondary endpoints included RBC-TI ≥ 8 and ≥ 12 wks (Wks 1–24), modified erythroid hematologic improvement (mHI-E; Wks 1–24), and safety. Efficacy by subgroups was assessed. Results: At cutoff (Oct 1, 2025), 106 pts (ESA-naive, n = 54; ESA-R/R/I, n = 52) received ≥ 1 LUSPA dose; median age was 76.0 y in both cohorts. Median (IQR) time since diagnosis was 2.2 (0.3–9.2) and 25.2 (10.0–65.5) mos in the ESA-naive and ESA-R/R/I cohorts, respectively. Median (IQR) follow-up was 11.1 (7.7–13.7) and 11.7 (9.2–14.3) mos; 51.9% and 57.7% had an SF3B1 mutation; 42.6% and 36.5% had ring sideroblast–negative (RS–) status; and 77.8% and 44.2% had baseline (BL) serum erythropoietin (sEPO) ≤ 200 IU/L, respectively. ESA-naive pts: PE was achieved in 81.5% of pts; RBC-TI ≥ 8 wks in 83.3% and ≥ 12 wks in 75.9%. RBC-TI ≥ 12 wks was achieved in 73.9% of RS– pts and 86.0% of BL sEPO ≤ 200 IU/L pts. mHI-E was achieved in 87.0% of pts. At cutoff, 70.4% of pts remained on tx, 1.9% completed, and 27.8% discontinued (11.1% from lack of efficacy). Median tx duration was 47.3 (range, 10.7–71.1) wks; 24.1% of pts had ≥ 1 dose reduction; 51.9% had ≥ 1 dose delay. Any grade tx-emergent adverse events (TEAEs) occurred in 94.4% of pts (29.6% tx-related); 20.4% led to tx interruption; grade 3/4 TEAEs occurred in 68.5% (11.1% tx-related). HR-MDS progression occurred in 3.7% of pts; none progressed to AML. ESA-R/R/I pts: PE was achieved in 61.5% of pts; RBC-TI ≥ 8 wks in 67.3% and ≥ 12 wks in 50.0%. RBC-TI ≥12 wks was achieved in 36.8% of RS– pts and 56.5% of BL sEPO ≤ 200 IU/L pts. mHI-E was achieved in 76.9% of pts. At cutoff, 38.5% of pts remained on tx, 1.9% completed, and 59.6% discontinued (23.1% from lack of efficacy). Median tx duration was 43.4 (range, 2.1–97.1) wks; 9.6% of pts had ≥ 1 dose reduction; 42.3% had ≥ 1 dose delay. Any grade TEAEs occurred in 100% of pts (46.2% tx-related); 21.2% led to tx interruption; grade 3/4 TEAEs occurred in 53.8% (7.7% tx-related). HR-MDS progression occurred in 3.8% of pts; none progressed to AML. Discussion and Conclusions: With 11 mos follow-up, LUSPA initiated at 1.75 mg/kg led to high, sustained PE achievement in both cohorts. Sustained RBC-TI ≥12 wks occurred in pts with RS– status and low BL sEPO. RBC-TI and mHI-E were notable in both cohorts. 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.", "abstract_shown": true, "affiliations": [ "Bristol Myers Squib, São Paulo, SP, Brazil", "Cancer Center Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy", "University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Spain", "MDS Unit, Hematology, University of Florence (Unifi), Italy", "Sunnybrook Health Sciences Centre, Canada", "Service Hématologie Séniors, Hôpital Saint-Louis (AP-HP), France", "West Virigina University (WVU) Cancer Institute, Wheeling Hospital, United States", "Bristol Myers Squibb, United States", "Bristol Myers Squibb, Switzerland", "Oncology and Internal Medicine, Medical University of Warsaw (MUW), Poland", "Willamette Valley Cancer Institute (WVCI), United States", "Algemeen Ziekenhuis (AZ) Delta Roeselare, Belgium", "Nice University Hospital, France", "Hospital Universitari Vall d’Hebron, Spain", "Service d’Hématologie, Centre Hospitalier Universitaire (CHU) de Poitiers, France", "Silesian Medical University (SUM), Poland", "Medical Oncology, Internal Medicine, Onkologie am Raschplatz (OaR), Germany", "University Hospital Leipzig (UKL), Germany", "Sylvester Comprehensive Cancer Center, University of Miami (UM), United States", "Yale University School of Medicine (YSM), United State" ], "article_type": null, "arxiv": null, "author_total": 21, "authors": [ { "affs": [ 0 ], "name": "Thais Herrero GERALDINO" }, { "affs": [ 1 ], "name": "Matteo Giovanni DELLA PORTA" }, { "affs": [ 2 ], "name": "Maria Diaz CAMPELO" }, { "affs": [ 3 ], "name": "Valeria SANTINI" }, { "affs": [ 4 ], "name": "Rena BUCKSTEIN" }, { "affs": [ 5 ], "name": "Lionel ADÈS" }, { "affs": [ 6 ], "name": "Bhavana BHATNAGAR" }, { "affs": [ 7 ], "name": "Yinzhi LAI" }, { "affs": [ 8 ], "name": "Dimana MITEVA" }, { "affs": [ 7 ], "name": "Ali MCBRIDE" }, { "affs": [ 9 ], "name": "Krzysztof MADRY" }, { "affs": [ 10 ], "name": "Luke FLETCHER" }, { "affs": [ 11 ], "name": "Dries DEEREN" }, { "affs": [ 12 ], "name": "Thomas CLUZEAU" }, { "affs": [ 13 ], "name": "David VALCÁRCEL" }, { "affs": [ 14 ], "name": "Jose Miguel TORREGROSA-DIAZ" }, { "affs": [ 15 ], "name": "Sebastian GROSICKI" }, { "affs": [ 16 ], "name": "Eyck VON DER HEYDE" }, { "affs": [ 17 ], "name": "Uwe PLATZBECKER" }, { "affs": [ 18 ], "name": "Sangeetha VENUGOPAL" }, { "affs": [ 19 ], "name": "Amer M ZEIDAN" } ], "bibtex": "https://research.draconitic.com/paper/58azs1v478yqs.bib", "cited_by": 0, "doi": "10.1016/j.htct.2026.107957", "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926017049", "id": "58azs1v478yqs", "issns": [ "2531-1379", "2531-1387" ], "landing_url": "https://doi.org/10.1016/j.htct.2026.107957", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RC633-647.5" ], [ "openalex", "2720|Acute Myeloid Leukemia Research" ] ], "openalex": "W7223094792", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-10-23", "publisher": "Elsevier", "ris": "https://research.draconitic.com/paper/58azs1v478yqs.ris", "sources": [ { "first_seen": "2026-10-30T12:17:17Z", "native_id": "0237116400004f07ac83c8c533c0e417", "source": "doaj", "url": "https://doi.org/10.1016/j.htct.2026.107957" } ], "subjects": [ { "field": "medicine", "origin": "lcc:RC633-647.5", "subfield": "endocrinology-metabolism" } ], "title": "LUSPATERCEPT INITIATED AT THE MAXIMUM-APPROVED DOSE IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO REQUIRE TRANSFUSIONS: PRIMARY ANALYSIS FROM MAXILUS", "title_text": "LUSPATERCEPT INITIATED AT THE MAXIMUM-APPROVED DOSE IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO REQUIRE TRANSFUSIONS: PRIMARY ANALYSIS FROM MAXILUS", "type": "peer-reviewed", "updated_at": "2026-10-30T13:43:18Z", "url": "https://research.draconitic.com/paper/58azs1v478yqs", "venue": "Hematology, Transfusion and Cell Therapy", "versions": [] }