{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:59:27Z","timestamp":1789012767530,"version":"build-2803163510"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>Patients with RRMM refractory to pomalidomide and\/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class\u2013refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class\u2013refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade \u2265 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3\/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3\/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1\/2 (93%); none were grade 4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class\u2013refractory and extramedullary disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.20.02259","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T16:56:20Z","timestamp":1607532980000},"page":"757-767","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":142,"title":["Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma"],"prefix":"10.1200","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-8865","authenticated-orcid":false,"given":"Paul G.","family":"Richardson","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Oriol","sequence":"additional","affiliation":[{"name":"Institut Catal\u00e0 d'Oncologia and Josep Carreras Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Larocca","sequence":"additional","affiliation":[{"name":"Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Citt\u00e0 della Salute e della Scienza, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Blad\u00e9","sequence":"additional","affiliation":[{"name":"Hematology Department, IDIBAPS, Hospital Clinic, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cavo","sequence":"additional","affiliation":[{"name":"Ser\u00e0gnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Rodriguez-Otero","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-4170","authenticated-orcid":false,"given":"Xavier","family":"Leleu","sequence":"additional","affiliation":[{"name":"CHU de Poitiers, Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Hiemenz","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, University of Florida, Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Hassoun","sequence":"additional","affiliation":[{"name":"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-2575","authenticated-orcid":false,"given":"Cyrille","family":"Touzeau","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Universit\u00e9 d'Angers, Universit\u00e9 de Nantes, Nantes, France"},{"name":"Site de Recherche Int\u00e9gr\u00e9e sur le Cancer (SIRIC), Imaging and Longitudinal Investigations to Ameliorate Decision-making (ILIAD), Nantes, France"},{"name":"Service d'h\u00e9matologie Clinique, Centre Hospitalier Universitaire, Place Alexis Ricordeau, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Alegre","sequence":"additional","affiliation":[{"name":"Hospital Universitario La Princesa and Hospital Universitario Quironsalud, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agne","family":"Paner","sequence":"additional","affiliation":[{"name":"Rush University Medical Center, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Maisel","sequence":"additional","affiliation":[{"name":"Baylor Scott & White Charles A. Sammons Cancer Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitabha","family":"Mazumder","sequence":"additional","affiliation":[{"name":"The Oncology Institute of Hope and Innovation, Glendale, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Raptis","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan S.","family":"Moreb","sequence":"additional","affiliation":[{"name":"Novant Health Hematology, Novant Health Forsyth Medical Center, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6418-0886","authenticated-orcid":false,"given":"Kenneth C.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-2052","authenticated-orcid":false,"given":"Jacob P.","family":"Laubach","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Thuresson","sequence":"additional","affiliation":[{"name":"Oncopeptides AB, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-9365","authenticated-orcid":false,"given":"Marcus","family":"Thuresson","sequence":"additional","affiliation":[{"name":"Oncopeptides AB, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1816-4172","authenticated-orcid":false,"given":"Catriona","family":"Byrne","sequence":"additional","affiliation":[{"name":"Oncopeptides AB, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-6130","authenticated-orcid":false,"given":"Johan","family":"Harmenberg","sequence":"additional","affiliation":[{"name":"Oncopeptides AB, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas A.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Oncopeptides AB, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Victoria","family":"Mateos","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universitario de Salamanca\/IBSAL\/CIC, Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the HORIZON (OP-106) Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"box1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.138"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx096"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0435-7"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13217"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2017.1.508"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.329"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-007-9092-1"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3752"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.07.026"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14065"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18420"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12020407"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2010.01826.x"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0735"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(20)30044-2"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-299487"},{"key":"b19","volume-title":"Statistical methods for rates and proportions","author":"Fleiss JL","year":"1981","edition":"2"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.2307\/2530286"},{"key":"b21","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(96)00075-X"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-631200"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903455"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-705210"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-016-0040-7"},{"key":"b26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817226"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-700872"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30788-0"},{"key":"b29","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2019.09.080"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32556-5"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70440-1"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0141-0"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2020-0024"},{"key":"b34","volume":"133","author":"Ocio EM","year":"2019","journal-title":"Blood"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.20.02259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T03:03:23Z","timestamp":1653793403000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.20.02259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,3,1]]}},"alternative-id":["10.1200\/JCO.20.02259"],"URL":"https:\/\/doi.org\/10.1200\/jco.20.02259","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,1]]},"assertion":[{"value":"2020-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-14","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}