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
Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with l...
Gespeichert in:
| Veröffentlicht in: | The Lancet (British edition) 2023-07, Vol.402 (10399), p.373-385, Article 373 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 385 |
|---|---|
| container_issue | 10399 |
| container_start_page | 373 |
| container_title | The Lancet (British edition) |
| container_volume | 402 |
| creator | Platzbecker, Uwe Della Porta, Matteo Giovanni Santini, Valeria Zeidan, Amer M Komrokji, Rami S Shortt, Jake Valcarcel, David Jonasova, Anna Dimicoli-Salazar, Sophie Tiong, Ing Soo Lin, Chien-Chin Li, Jiahui Zhang, Jennie Giuseppi, Ana Carolina Kreitz, Sandra Pozharskaya, Veronika Keeperman, Karen L Rose, Shelonitda Shetty, Jeevan K Hayati, Sheida Vodala, Sadanand Prebet, Thomas Degulys, Andrius Paolini, Stefania Cluzeau, Thomas Fenaux, Pierre Garcia-Manero, Guillermo |
| description | Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.
The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2–6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (200 to |
| doi_str_mv | 10.1016/S0140-6736(23)00874-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2825810636</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0140673623008747</els_id><sourcerecordid>2842928267</sourcerecordid><originalsourceid>FETCH-LOGICAL-c445t-d7005c961519b8200f02a74e2f5ebc4b27b4975ba27e6545555daab50a38d6043</originalsourceid><addsrcrecordid>eNqFks9u1DAQxiMEosvCI4AscdlKG3ASO8nCAVVL-SO19FCQuFkTe9K6OHGwnUV5bN4Ap1v2UAnhy1jyb775PDNJ8jyjrzKala8vacZoWlZFucqLY0rriqXVg2SRsXjhrPr-MFkckKPkifc3lFJWUv44OSqqIstYWS-S36dtqyXIiUCviIcWw0RsS8zoBwjoJA6B7ND50RMcLAbdEzAtkBjRTeHa2cFq9NqnPuhuNBCJKwJX2Ie0B73DNQkOet-OXts-VThgr-Ljmhj7C13qtP9BugmNVZMfDEQVSfzUK2c79GS1vTg_P_ny_vL4TSwZDekuOgUzxYqzTyDDNXgkxZrYqJwaaNCsSayobKc9KiJtH5w1Jl6D02CeJo9aMB6f3cVl8u3D6dftp_Ts4uPn7clZKhnjIVUVpVxuyoxnm6bOKW1pDhXDvOXYSNbkVcM2FW8gr7DkjMejABpOoahVSVmxTFZ73cHZnyP6IKIficZAj3b0Iq9zXme0LMqIvryH3tjRxV_OFMs3EY1TXCZ8T0lnvXfYiiF2A9wkMirmnRC3OyHmgYu8ELc7Iea8F3fqY9OhOmT9XYIIvL0nLHWIc5wbB9oc5P0_5N_tszE2c6fRCS819hKVdiiDUFb_x-AfzbbePA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2842928267</pqid></control><display><type>article</type><title>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</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><source>ProQuest Central UK/Ireland</source><creator>Platzbecker, Uwe ; Della Porta, Matteo Giovanni ; Santini, Valeria ; Zeidan, Amer M ; Komrokji, Rami S ; Shortt, Jake ; Valcarcel, David ; Jonasova, Anna ; Dimicoli-Salazar, Sophie ; Tiong, Ing Soo ; Lin, Chien-Chin ; Li, Jiahui ; Zhang, Jennie ; Giuseppi, Ana Carolina ; Kreitz, Sandra ; Pozharskaya, Veronika ; Keeperman, Karen L ; Rose, Shelonitda ; Shetty, Jeevan K ; Hayati, Sheida ; Vodala, Sadanand ; Prebet, Thomas ; Degulys, Andrius ; Paolini, Stefania ; Cluzeau, Thomas ; Fenaux, Pierre ; Garcia-Manero, Guillermo</creator><creatorcontrib>Platzbecker, Uwe ; Della Porta, Matteo Giovanni ; Santini, Valeria ; Zeidan, Amer M ; Komrokji, Rami S ; Shortt, Jake ; Valcarcel, David ; Jonasova, Anna ; Dimicoli-Salazar, Sophie ; Tiong, Ing Soo ; Lin, Chien-Chin ; Li, Jiahui ; Zhang, Jennie ; Giuseppi, Ana Carolina ; Kreitz, Sandra ; Pozharskaya, Veronika ; Keeperman, Karen L ; Rose, Shelonitda ; Shetty, Jeevan K ; Hayati, Sheida ; Vodala, Sadanand ; Prebet, Thomas ; Degulys, Andrius ; Paolini, Stefania ; Cluzeau, Thomas ; Fenaux, Pierre ; Garcia-Manero, Guillermo</creatorcontrib><description>Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.
The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2–6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1–24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).
Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years [IQR 69–80]). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8–37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks [IQR 20–73]) versus epoetin alfa (27 weeks [19–55]). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).
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.
Celgene and Acceleron Pharma.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(23)00874-7</identifier><identifier>PMID: 37311468</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acute myeloid leukemia ; Adverse events ; Aged ; Anemia ; Anemia - drug therapy ; Anemia - etiology ; Asthenia ; Blood ; Blood transfusion ; Body Weight ; Bone marrow ; Clinical trials ; Commands ; COVID-19 ; Diagnosis ; Disorders ; Drug dosages ; Dyspnea ; Dyspnea - drug therapy ; Effectiveness ; Epoetin Alfa - adverse effects ; Erythrocytes ; Erythropoiesis ; Erythropoietin ; Female ; Hematinics - adverse effects ; Hemoglobin ; Hemoglobins - therapeutic use ; Humans ; Hypertension ; Hypertension - drug therapy ; Leukemia ; Male ; Myelodysplastic syndrome ; Myelodysplastic syndromes ; Myelodysplastic Syndromes - chemically induced ; Myelodysplastic Syndromes - complications ; Myelodysplastic Syndromes - drug therapy ; Neutropenia ; Patients ; Pharmaceuticals ; Pneumonia ; Randomization ; Respiration ; Response rates ; Risk ; Safety ; Subgroups ; Syncope ; Thrombocytopenia ; Titration ; Transfusion</subject><ispartof>The Lancet (British edition), 2023-07, Vol.402 (10399), p.373-385, Article 373</ispartof><rights>2023 Elsevier Ltd</rights><rights>Copyright © 2023 Elsevier Ltd. All rights reserved.</rights><rights>2023. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-d7005c961519b8200f02a74e2f5ebc4b27b4975ba27e6545555daab50a38d6043</citedby><cites>FETCH-LOGICAL-c445t-d7005c961519b8200f02a74e2f5ebc4b27b4975ba27e6545555daab50a38d6043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2842928267?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000,64390,64392,64394,72474</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37311468$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Platzbecker, Uwe</creatorcontrib><creatorcontrib>Della Porta, Matteo Giovanni</creatorcontrib><creatorcontrib>Santini, Valeria</creatorcontrib><creatorcontrib>Zeidan, Amer M</creatorcontrib><creatorcontrib>Komrokji, Rami S</creatorcontrib><creatorcontrib>Shortt, Jake</creatorcontrib><creatorcontrib>Valcarcel, David</creatorcontrib><creatorcontrib>Jonasova, Anna</creatorcontrib><creatorcontrib>Dimicoli-Salazar, Sophie</creatorcontrib><creatorcontrib>Tiong, Ing Soo</creatorcontrib><creatorcontrib>Lin, Chien-Chin</creatorcontrib><creatorcontrib>Li, Jiahui</creatorcontrib><creatorcontrib>Zhang, Jennie</creatorcontrib><creatorcontrib>Giuseppi, Ana Carolina</creatorcontrib><creatorcontrib>Kreitz, Sandra</creatorcontrib><creatorcontrib>Pozharskaya, Veronika</creatorcontrib><creatorcontrib>Keeperman, Karen L</creatorcontrib><creatorcontrib>Rose, Shelonitda</creatorcontrib><creatorcontrib>Shetty, Jeevan K</creatorcontrib><creatorcontrib>Hayati, Sheida</creatorcontrib><creatorcontrib>Vodala, Sadanand</creatorcontrib><creatorcontrib>Prebet, Thomas</creatorcontrib><creatorcontrib>Degulys, Andrius</creatorcontrib><creatorcontrib>Paolini, Stefania</creatorcontrib><creatorcontrib>Cluzeau, Thomas</creatorcontrib><creatorcontrib>Fenaux, Pierre</creatorcontrib><creatorcontrib>Garcia-Manero, Guillermo</creatorcontrib><title>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</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.
The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2–6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1–24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).
Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years [IQR 69–80]). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8–37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks [IQR 20–73]) versus epoetin alfa (27 weeks [19–55]). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).
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.
Celgene and Acceleron Pharma.</description><subject>Acute myeloid leukemia</subject><subject>Adverse events</subject><subject>Aged</subject><subject>Anemia</subject><subject>Anemia - drug therapy</subject><subject>Anemia - etiology</subject><subject>Asthenia</subject><subject>Blood</subject><subject>Blood transfusion</subject><subject>Body Weight</subject><subject>Bone marrow</subject><subject>Clinical trials</subject><subject>Commands</subject><subject>COVID-19</subject><subject>Diagnosis</subject><subject>Disorders</subject><subject>Drug dosages</subject><subject>Dyspnea</subject><subject>Dyspnea - drug therapy</subject><subject>Effectiveness</subject><subject>Epoetin Alfa - adverse effects</subject><subject>Erythrocytes</subject><subject>Erythropoiesis</subject><subject>Erythropoietin</subject><subject>Female</subject><subject>Hematinics - adverse effects</subject><subject>Hemoglobin</subject><subject>Hemoglobins - therapeutic use</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - drug therapy</subject><subject>Leukemia</subject><subject>Male</subject><subject>Myelodysplastic syndrome</subject><subject>Myelodysplastic syndromes</subject><subject>Myelodysplastic Syndromes - chemically induced</subject><subject>Myelodysplastic Syndromes - complications</subject><subject>Myelodysplastic Syndromes - drug therapy</subject><subject>Neutropenia</subject><subject>Patients</subject><subject>Pharmaceuticals</subject><subject>Pneumonia</subject><subject>Randomization</subject><subject>Respiration</subject><subject>Response rates</subject><subject>Risk</subject><subject>Safety</subject><subject>Subgroups</subject><subject>Syncope</subject><subject>Thrombocytopenia</subject><subject>Titration</subject><subject>Transfusion</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFks9u1DAQxiMEosvCI4AscdlKG3ASO8nCAVVL-SO19FCQuFkTe9K6OHGwnUV5bN4Ap1v2UAnhy1jyb775PDNJ8jyjrzKala8vacZoWlZFucqLY0rriqXVg2SRsXjhrPr-MFkckKPkifc3lFJWUv44OSqqIstYWS-S36dtqyXIiUCviIcWw0RsS8zoBwjoJA6B7ND50RMcLAbdEzAtkBjRTeHa2cFq9NqnPuhuNBCJKwJX2Ie0B73DNQkOet-OXts-VThgr-Ljmhj7C13qtP9BugmNVZMfDEQVSfzUK2c79GS1vTg_P_ny_vL4TSwZDekuOgUzxYqzTyDDNXgkxZrYqJwaaNCsSayobKc9KiJtH5w1Jl6D02CeJo9aMB6f3cVl8u3D6dftp_Ts4uPn7clZKhnjIVUVpVxuyoxnm6bOKW1pDhXDvOXYSNbkVcM2FW8gr7DkjMejABpOoahVSVmxTFZ73cHZnyP6IKIficZAj3b0Iq9zXme0LMqIvryH3tjRxV_OFMs3EY1TXCZ8T0lnvXfYiiF2A9wkMirmnRC3OyHmgYu8ELc7Iea8F3fqY9OhOmT9XYIIvL0nLHWIc5wbB9oc5P0_5N_tszE2c6fRCS819hKVdiiDUFb_x-AfzbbePA</recordid><startdate>20230729</startdate><enddate>20230729</enddate><creator>Platzbecker, Uwe</creator><creator>Della Porta, Matteo Giovanni</creator><creator>Santini, Valeria</creator><creator>Zeidan, Amer M</creator><creator>Komrokji, Rami S</creator><creator>Shortt, Jake</creator><creator>Valcarcel, David</creator><creator>Jonasova, Anna</creator><creator>Dimicoli-Salazar, Sophie</creator><creator>Tiong, Ing Soo</creator><creator>Lin, Chien-Chin</creator><creator>Li, Jiahui</creator><creator>Zhang, Jennie</creator><creator>Giuseppi, Ana Carolina</creator><creator>Kreitz, Sandra</creator><creator>Pozharskaya, Veronika</creator><creator>Keeperman, Karen L</creator><creator>Rose, Shelonitda</creator><creator>Shetty, Jeevan K</creator><creator>Hayati, Sheida</creator><creator>Vodala, Sadanand</creator><creator>Prebet, Thomas</creator><creator>Degulys, Andrius</creator><creator>Paolini, Stefania</creator><creator>Cluzeau, Thomas</creator><creator>Fenaux, Pierre</creator><creator>Garcia-Manero, Guillermo</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20230729</creationdate><title>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</title><author>Platzbecker, Uwe ; Della Porta, Matteo Giovanni ; Santini, Valeria ; Zeidan, Amer M ; Komrokji, Rami S ; Shortt, Jake ; Valcarcel, David ; Jonasova, Anna ; Dimicoli-Salazar, Sophie ; Tiong, Ing Soo ; Lin, Chien-Chin ; Li, Jiahui ; Zhang, Jennie ; Giuseppi, Ana Carolina ; Kreitz, Sandra ; Pozharskaya, Veronika ; Keeperman, Karen L ; Rose, Shelonitda ; Shetty, Jeevan K ; Hayati, Sheida ; Vodala, Sadanand ; Prebet, Thomas ; Degulys, Andrius ; Paolini, Stefania ; Cluzeau, Thomas ; Fenaux, Pierre ; Garcia-Manero, Guillermo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-d7005c961519b8200f02a74e2f5ebc4b27b4975ba27e6545555daab50a38d6043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acute myeloid leukemia</topic><topic>Adverse events</topic><topic>Aged</topic><topic>Anemia</topic><topic>Anemia - drug therapy</topic><topic>Anemia - etiology</topic><topic>Asthenia</topic><topic>Blood</topic><topic>Blood transfusion</topic><topic>Body Weight</topic><topic>Bone marrow</topic><topic>Clinical trials</topic><topic>Commands</topic><topic>COVID-19</topic><topic>Diagnosis</topic><topic>Disorders</topic><topic>Drug dosages</topic><topic>Dyspnea</topic><topic>Dyspnea - drug therapy</topic><topic>Effectiveness</topic><topic>Epoetin Alfa - adverse effects</topic><topic>Erythrocytes</topic><topic>Erythropoiesis</topic><topic>Erythropoietin</topic><topic>Female</topic><topic>Hematinics - adverse effects</topic><topic>Hemoglobin</topic><topic>Hemoglobins - therapeutic use</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - drug therapy</topic><topic>Leukemia</topic><topic>Male</topic><topic>Myelodysplastic syndrome</topic><topic>Myelodysplastic syndromes</topic><topic>Myelodysplastic Syndromes - chemically induced</topic><topic>Myelodysplastic Syndromes - complications</topic><topic>Myelodysplastic Syndromes - drug therapy</topic><topic>Neutropenia</topic><topic>Patients</topic><topic>Pharmaceuticals</topic><topic>Pneumonia</topic><topic>Randomization</topic><topic>Respiration</topic><topic>Response rates</topic><topic>Risk</topic><topic>Safety</topic><topic>Subgroups</topic><topic>Syncope</topic><topic>Thrombocytopenia</topic><topic>Titration</topic><topic>Transfusion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Platzbecker, Uwe</creatorcontrib><creatorcontrib>Della Porta, Matteo Giovanni</creatorcontrib><creatorcontrib>Santini, Valeria</creatorcontrib><creatorcontrib>Zeidan, Amer M</creatorcontrib><creatorcontrib>Komrokji, Rami S</creatorcontrib><creatorcontrib>Shortt, Jake</creatorcontrib><creatorcontrib>Valcarcel, David</creatorcontrib><creatorcontrib>Jonasova, Anna</creatorcontrib><creatorcontrib>Dimicoli-Salazar, Sophie</creatorcontrib><creatorcontrib>Tiong, Ing Soo</creatorcontrib><creatorcontrib>Lin, Chien-Chin</creatorcontrib><creatorcontrib>Li, Jiahui</creatorcontrib><creatorcontrib>Zhang, Jennie</creatorcontrib><creatorcontrib>Giuseppi, Ana Carolina</creatorcontrib><creatorcontrib>Kreitz, Sandra</creatorcontrib><creatorcontrib>Pozharskaya, Veronika</creatorcontrib><creatorcontrib>Keeperman, Karen L</creatorcontrib><creatorcontrib>Rose, Shelonitda</creatorcontrib><creatorcontrib>Shetty, Jeevan K</creatorcontrib><creatorcontrib>Hayati, Sheida</creatorcontrib><creatorcontrib>Vodala, Sadanand</creatorcontrib><creatorcontrib>Prebet, Thomas</creatorcontrib><creatorcontrib>Degulys, Andrius</creatorcontrib><creatorcontrib>Paolini, Stefania</creatorcontrib><creatorcontrib>Cluzeau, Thomas</creatorcontrib><creatorcontrib>Fenaux, Pierre</creatorcontrib><creatorcontrib>Garcia-Manero, Guillermo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>News PRO</collection><collection>Pharma and Biotech Premium PRO</collection><collection>Global News & ABI/Inform Professional</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>British Nursing Index</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Newsstand Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Science Database (ProQuest)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Platzbecker, Uwe</au><au>Della Porta, Matteo Giovanni</au><au>Santini, Valeria</au><au>Zeidan, Amer M</au><au>Komrokji, Rami S</au><au>Shortt, Jake</au><au>Valcarcel, David</au><au>Jonasova, Anna</au><au>Dimicoli-Salazar, Sophie</au><au>Tiong, Ing Soo</au><au>Lin, Chien-Chin</au><au>Li, Jiahui</au><au>Zhang, Jennie</au><au>Giuseppi, Ana Carolina</au><au>Kreitz, Sandra</au><au>Pozharskaya, Veronika</au><au>Keeperman, Karen L</au><au>Rose, Shelonitda</au><au>Shetty, Jeevan K</au><au>Hayati, Sheida</au><au>Vodala, Sadanand</au><au>Prebet, Thomas</au><au>Degulys, Andrius</au><au>Paolini, Stefania</au><au>Cluzeau, Thomas</au><au>Fenaux, Pierre</au><au>Garcia-Manero, Guillermo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2023-07-29</date><risdate>2023</risdate><volume>402</volume><issue>10399</issue><spage>373</spage><epage>385</epage><pages>373-385</pages><artnum>373</artnum><issn>0140-6736</issn><eissn>1474-547X</eissn><abstract>Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.
The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2–6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1–24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).
Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years [IQR 69–80]). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8–37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks [IQR 20–73]) versus epoetin alfa (27 weeks [19–55]). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).
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.
Celgene and Acceleron Pharma.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>37311468</pmid><doi>10.1016/S0140-6736(23)00874-7</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2023-07, Vol.402 (10399), p.373-385, Article 373 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2825810636 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete; ProQuest Central UK/Ireland |
| subjects | Acute myeloid leukemia Adverse events Aged Anemia Anemia - drug therapy Anemia - etiology Asthenia Blood Blood transfusion Body Weight Bone marrow Clinical trials Commands COVID-19 Diagnosis Disorders Drug dosages Dyspnea Dyspnea - drug therapy Effectiveness Epoetin Alfa - adverse effects Erythrocytes Erythropoiesis Erythropoietin Female Hematinics - adverse effects Hemoglobin Hemoglobins - therapeutic use Humans Hypertension Hypertension - drug therapy Leukemia Male Myelodysplastic syndrome Myelodysplastic syndromes Myelodysplastic Syndromes - chemically induced Myelodysplastic Syndromes - complications Myelodysplastic Syndromes - drug therapy Neutropenia Patients Pharmaceuticals Pneumonia Randomization Respiration Response rates Risk Safety Subgroups Syncope Thrombocytopenia Titration Transfusion |
| title | 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T15%3A46%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20safety%20of%20luspatercept%20versus%20epoetin%20alfa%20in%20erythropoiesis-stimulating%20agent-naive,%20transfusion-dependent,%20lower-risk%20myelodysplastic%20syndromes%20(COMMANDS):%20interim%20analysis%20of%20a%20phase%203,%20open-label,%20randomised%20controlled%20trial&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Platzbecker,%20Uwe&rft.date=2023-07-29&rft.volume=402&rft.issue=10399&rft.spage=373&rft.epage=385&rft.pages=373-385&rft.artnum=373&rft.issn=0140-6736&rft.eissn=1474-547X&rft_id=info:doi/10.1016/S0140-6736(23)00874-7&rft_dat=%3Cproquest_cross%3E2842928267%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2842928267&rft_id=info:pmid/37311468&rft_els_id=S0140673623008747&rfr_iscdi=true |