Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study
| العنوان: | Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study |
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| المؤلفون: | Fredrik H Schjesvold, Meletios-Athanasios Dimopoulos, Sosana Delimpasi, Pawel Robak, Daniel Coriu, Wojciech Legiec, Luděk Pour, Ivan Špička, Tamas Masszi, Vadim Doronin, Jiri Minarik, Galina Salogub, Yulia Alekseeva, Antonio Lazzaro, Vladimir Maisnar, Gábor Mikala, Laura Rosiñol, Anna Marina Liberati, Argiris Symeonidis, Victoria Moody, Marcus Thuresson, Catriona Byrne, Johan Harmenberg, Nicolaas A Bakker, Roman Hájek, Maria-Victoria Mateos, Paul G Richardson, Pieter Sonneveld, Fredrik Schjesvold, Anna Nikolayeva, Waldemar Tomczak, Ludek Pour, Ivan Spicka, Gabor Mikala, Laura Rosinol, Tatiana Konstantinova, Anargyros Symeonidis, Moshe Gatt, Arpad Illes, Haifaa Abdulhaq, Moez Dungarwalla, Sebastian Grosicki, Roman Hajek, Xavier Leleu, Alexander Myasnikov, Paul G. Richardson, Irit Avivi, Dries Deeren, Mercedes Gironella, Miguel Teodoro Hernandez-Garcia, Joaquin Martinez Lopez, Muriel Newinger-Porte, Paz Ribas, Olga Samoilova, Eric Voog, Mario Arnao-Herraiz, Estrella Carrillo-Cruz, Paolo Corradini, Jyothi Dodlapati, Miquel Granell Gorrochategui, Shang-Yi Huang, Matthew Jenner, Lionel Karlin, Jin Seok Kim, Agnieszka Kopacz, Nadezhda Medvedeva, Chang-Ki Min, Roberto Mina, Katrin Palk, Ho-Jin Shin, Sang Kyun Sohn, Jason Tache, Achilles Anagnostopoulos, Jose-Maria Arguiñano, Michele Cavo, Joanne Filicko, Margaret Garnes, Janusz Halka, Kathrin Herzog-Tzarfati, Natalia Ipatova, Kihyun Kim, Maria-Theresa Krauth, Irina Kryuchkova, Mihaela Cornelia Lazaroiu, Mario Luppi, Andrei Proydakov, Alessandro Rambaldi, Milda Rudzianskiene, Su-Peng Yeh, Maria Magdalena Alcalá-Peña, Adrian Alegre Amor, Hussain Alizadeh, Maurizio Bendandi, Gillian Brearton, Randall Brown, Jim Cavet, Najib Dally, Miklos Egyed, José Ángel Hernández-Rivas, Ain Kaare, Jean-Michel Karsenti, Janusz Kloczko, William Kreisle, Je-Jung Lee, Sigrid Machherndl-Spandl, Sudhir Manda, Ivan Moiseev, Jan Moreb, Zsolt Nagy, Santosh Nair, Albert Oriol-Rocafiguera, Michael Osswald, Paula Otero-Rodriguez, Valdas Peceliunas, Torben Plesner, Philippe Rey, Giuseppe Rossi, Don Stevens, Celia Suriu, Corrado Tarella, Anke Verlinden, Alain Zannetti |
| المساهمون: | Hematology, Oncopeptides |
| المصدر: | The Lancet Haematology, 9(2), e98-e110. Lancet Publishing Group Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Elsevier BV, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Published Online, See Comment page e82, Malignancies, University of, Department of Hematology, Hematology |
| الوصف: | Background Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. Methods In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0–2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. Findings Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60–72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61–72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0–8·5; 165 [67%] of 246 patients had an event) in the melflufen group and 4·9 months (4·2–5·7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0·79, [95% CI 0·64–0·98]; p=0·032), at a median follow-up of 15·5 months (IQR 9·4–22·8) in the melflufen group and 16·3 months (10·1–23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1–25·6) at a median follow-up of 19·8 months (IQR 12·0–25·0) in the melflufen group and 25·0 months (95% CI 18·1–31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8–23·7; HR 1·10 [95% CI 0·85–1·44]; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs 102 [41%]), and anaemia (97 [43%] vs 44 [18%]). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]). 27 [12%] patients in the melflufen group and 32 [13%] in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia). Interpretation Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Oncopeptides AB |
| تدمد: | 2352-3026 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9dc03258e4b4010f40b43625027ef43bTest https://doi.org/10.1016/s2352-3026Test(21)00381-1 |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9dc03258e4b4010f40b43625027ef43b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523026 |
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