{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:02:02Z","timestamp":1791529322669,"version":"4.3.4"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Hematology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\u03b2-thalassemia is a hereditary blood disorder resulting in ineffective erythropoiesis and anemia. Management of anemia with regular blood transfusions is associated with complications including iron overload. Here, we report long-term safety and efficacy results of the first clinical study of luspatercept in \u03b2-thalassemia, initiated in 2013, enrolling adults with both nontransfusion-dependent (NTD) and transfusion-dependent (TD) \u03b2-thalassemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>The objective was to report long-term safety data, for up to 5\u2009years of treatment, for 64 patients with TD or NTD \u03b2-thalassemia, and long-term efficacy data for a subset of 63 patients with \u03b2-thalassemia who received high-dose luspatercept (0.6\u20131.25\u2009mg\/kg): 31 NTD and 32 TD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>The study was a phase 2, noncontrolled, open-label trial comprising a dose-finding base phase and a 5-year extension phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Endpoints include safety; erythroid response over a continuous 12-week period [NTD: hemoglobin increase from baseline \u2a7e1.0 or \u2a7e1.5 g\/dl; TD: red blood cell (RBC) transfusion burden reduction, \u2a7e20%, \u2a7e33%, or \u2a7e50%]; and changes in biomarkers of ineffective erythropoiesis, iron metabolism parameters, Functional Assessment of Chronic Illness Therapy \u2013 Fatigue (FACIT-F) scores, and 6-min walking distance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Median duration of luspatercept exposure for NTD and TD patients was 910\u2009days (range, 40\u20131850) and 433\u2009days (range, 21\u20131790), respectively. Seventeen of 31 (54.8%) NTD patients achieved a mean hemoglobin increase of \u2a7e1.5\u2009g\/dl and 19 of 32 (59.4%) TD patients achieved \u2a7e50% reduction in RBC transfusion burden, during any continuous 12-week period. Median cumulative duration of response was 1126\u2009days (range, 127\u20131790) for NTD patients and 909\u2009days (range, 87\u20131734) for TD patients. The most common treatment-related adverse events of any grade were bone pain, headache, and myalgia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Long-term assessment of patients with \u03b2-thalassemia showed luspatercept was associated with sustained increases in hemoglobin levels in NTD patients and sustained transfusion burden reductions in TD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>(ClinicalTrials.gov Identifiers: NCT01749540 and NCT02268409).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      Long-term safety and erythroid response with luspatercept treatment in patients with \u03b2-thalassemia Background: \u03b2-thalassemia is a genetic blood disorder caused by mutations in the \u03b2-globin gene, which encodes one of the proteins that comprise hemoglobin, a key constituent of red blood cells. Patients with \u03b2-thalassemia experience anemia, the main treatment for which is blood transfusions. Long-term repeated blood transfusions lower patients\u2019 quality of life, use hospital resources, and the resulting accumulation of excess iron can cause organ failure and decrease life expectancy. The severity of the anemia experienced by patients with \u03b2-thalassemia varies; patients with transfusion-dependent \u03b2-thalassemia require regular blood transfusions, compared with those with nontransfusion-dependent \u03b2-thalassemia who require infrequent transfusions, or even none at all, to manage their symptoms. Luspatercept (Reblozyl\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ) is an agent that stimulates the production of red blood cells and is used to treat anemia caused by \u03b2-thalassemia. However, the long-term effects of luspatercept treatment on patients with \u03b2-thalassemia are not known. Objective: In this study, we report the long-term safety of luspatercept in 64 adult patients with either transfusion-dependent or nontransfusion-dependent \u03b2-thalassemia, and the long-term efficacy of high-dose luspatercept (0.6\u20131.25\u2009mg\/kg) in a subset of 63 patients. Results: The average time period that patients were treated with luspatercept was 910\u2009days for nontransfusion-dependent \u03b2-thalassemia and 433\u2009days for transfusion-dependent \u03b2-thalassemia. We report that in patients with nontransfusion-dependent \u03b2-thalassemia, luspatercept treatment was associated with sustained increases, just over 3\u2009years, in hemoglobin levels. Likewise, in transfusion-dependent \u03b2-thalassemia, luspatercept treatment was associated with a sustained reduction, 2.5\u2009years, in the amount of blood transfusion required to manage their anemia. Long-term treatment with luspatercept was not associated with any new side effects compared with previous short-term treatment studies. The most common side effects were headache (27 patients), bone pain (20 patients), and muscle pain (14 patients) with more than 90% of these patients experiencing these side effects as mild severity. Conclusion: The results of this study show that in patients with either transfusion-dependent or nontransfusion-dependent \u03b2-thalassemia, luspatercept provides lasting reduction in anemia with mostly mild and predictable side effects.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20406207221134404","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T07:16:53Z","timestamp":1670224613000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Long-term safety and erythroid response with luspatercept treatment in patients with \u03b2-thalassemia"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-1899","authenticated-orcid":false,"given":"Antonio","family":"Piga","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, Turin University, Regione Gonzole, 10, Orbassano, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Turin University, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Gamberini","sequence":"additional","affiliation":[{"name":"Thalassemia Unit, Arcispedale S. Anna, Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersi","family":"Voskaridou","sequence":"additional","affiliation":[{"name":"Thalassemia and Sickle Cell Center, Laiko General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-3308","authenticated-orcid":false,"given":"Paolo","family":"Ricchi","sequence":"additional","affiliation":[{"name":"Malattie Rare Del Globulo Rosso, AORN Cardarelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Caruso","sequence":"additional","affiliation":[{"name":"ARNAS Garibaldi, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Pietrangelo","sequence":"additional","affiliation":[{"name":"CEMEF, Medicina 2, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosha","family":"Zhang","sequence":"additional","affiliation":[{"name":"Formerly Acceleron Pharma, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeevan K.","family":"Shetty","sequence":"additional","affiliation":[{"name":"Celgene International S\u00e0rl, Bristol-Myers Squibb Company, Boudry, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Attie","sequence":"additional","affiliation":[{"name":"Formerly Acceleron Pharma, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immacolata","family":"Tartaglione","sequence":"additional","affiliation":[{"name":"Universit\u00e0 della Campania \u201cL. Vanvitelli\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"bibr1-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1038\/35066048"},{"key":"bibr2-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011726"},{"key":"bibr3-20406207221134404","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.066845"},{"key":"bibr4-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2021838"},{"key":"bibr5-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2014-308112"},{"key":"bibr6-20406207221134404","first-page":"1187","volume":"89","author":"Borgna-Pignatti C","year":"2004","journal-title":"Haematologica"},{"key":"bibr7-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2017.1.272"},{"key":"bibr8-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26056"},{"key":"bibr9-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2011.01582.x"},{"key":"bibr10-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.100588"},{"key":"bibr11-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16753"},{"key":"bibr12-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1345.059"},{"key":"bibr13-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21896"},{"key":"bibr14-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.3633.3633"},{"key":"bibr15-20406207221134404","doi-asserted-by":"publisher","DOI":"10.47102\/annals-acadmedsg.V45N11p520"},{"key":"bibr16-20406207221134404","volume-title":"et al. 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Dublin: Bristol-Myers Squibb Pharma EEIG, https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/reblozyl-epar-product-information_en.pdf (2021, accessed May 2022)."},{"key":"bibr36-20406207221134404","unstructured":"REBLOZYL\u00ae (luspatercept-aamt) [prescribing information]. Princeton, NJ: Bristol Myers Squibb, https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2020\/761136orig2lbl.pdf (2020, accessed May 2022)."},{"key":"bibr37-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-06774-8"},{"key":"bibr38-20406207221134404","doi-asserted-by":"publisher","DOI":"10.1016\/j.hemonc.2017.02.002"}],"container-title":["Therapeutic Advances in Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207221134404","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20406207221134404","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207221134404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:16:22Z","timestamp":1777590982000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20406207221134404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":38,"alternative-id":["10.1177\/20406207221134404"],"URL":"https:\/\/doi.org\/10.1177\/20406207221134404","relation":{},"ISSN":["2040-6207","2040-6215"],"issn-type":[{"value":"2040-6207","type":"print"},{"value":"2040-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"article-number":"20406207221134404"}}