دورية أكاديمية
Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study.
| العنوان: | Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study. |
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| المؤلفون: | Pour L; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Babak Myeloma Group, Faculty of Medicine, Masaryk University, Brno, Czech Republic. pour.ludek@fnbrno.cz., Szarejko M; University Clinical Centre, Department of Hematology and Transplantology, Gdansk., Bila J; Clinic of Hematology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade., Schjesvold FH; Oslo Myeloma Center, Department of Hematology, Oslo University Hospital and KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo., Spicka I; 1st Department of Medicine - Department of Hematology, First Faculty of Medicine, Charles University and General Hospital in Prague, Prague, Czech Republic., Maisnar V; 4th Department of Medicine - Hematology, Charles University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic., Jurczyszyn A; Plasma Cell Dyscrasias Center, Department of Hematology, Jagiellonian University Faculty of Medicine, Krakow., Grudeva-Popova Z; Department of Clinical Oncology, Medical Faculty, Medical University of Plovdiv, Plovdic, Bulgaria., Hájek R; Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic., Usenko G; City Clinical Hospital No. 4 of Dnipro City Council, Dnipro, Ukraine., Thuresson M; Oncopeptides AB, Stockholm., Norin S; Oncopeptides AB, Stockholm., Jarefors S; Oncopeptides AB, Stockholm., Bakker NA; Oncopeptides AB, Stockholm., Richardson PG; Dana-Farber Cancer Institute, Boston, MA., Mateos MV; Hospital Clínico Universitario de Salamanca/IBSAL/CIC, Salamanca. |
| المصدر: | Haematologica [Haematologica] 2024 Mar 01; Vol. 109 (3), pp. 895-905. Date of Electronic Publication: 2024 Mar 01. |
| نوع المنشور: | Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Ferrata Storti Foundation Country of Publication: Italy NLM ID: 0417435 Publication Model: Electronic Cited Medium: Internet ISSN: 1592-8721 (Electronic) Linking ISSN: 03906078 NLM ISO Abbreviation: Haematologica Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Pavia, Italy : Ferrata Storti Foundation Original Publication: Pavia [etc.] |
| مواضيع طبية MeSH: | Antibodies, Monoclonal* , Hematopoietic Stem Cell Transplantation* , Melphalan*/analogs & derivatives , Multiple Myeloma*/diagnosis , Multiple Myeloma*/drug therapy , Neoplasms, Plasma Cell* , Neutropenia* , Phenylalanine*/analogs & derivatives, Humans ; Dexamethasone/therapeutic use ; Proteasome Inhibitors ; Transplantation, Autologous ; United States ; Antineoplastic Combined Chemotherapy Protocols/adverse effects |
| مستخلص: | Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone was approved in Europe for use in patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) with ≥3 prior lines of therapy and without prior autologous stem cell transplantation (ASCT) or with a time to progression >36 months after prior ASCT. The randomized LIGHTHOUSE study (NCT04649060) assessed melflufen plus daratumumab and dexamethasone (melflufen group) versus daratumumab in patients with RRMM with disease refractory to an immunomodulatory agent and a proteasome inhibitor or who had received ≥3 prior lines of therapy including an immunomodulatory agent and a proteasome inhibitor. A partial clinical hold issued by the US Food and Drug Administration for all melflufen studies led to financial constraints and premature study closure on February 23rd 2022 (data cut-off date). In total, 54 of 240 planned patients were randomized (melflufen group, N=27; daratumumab group, N=27). Median progression-free survival (PFS) was not reached in the melflufen group versus 4.9 months in the daratumumab group (Hazard Ratio: 0.18 [95% Confidence Interval, 0.05-0.65]; P=0.0032) at a median follow-up time of 7.1 and 6.6 months, respectively. Overall response rate (ORR) was 59% in the melflufen group versus 30% in the daratumumab group (P=0.0300). The most common grade ≥3 treatment-emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% vs. 12%), thrombocytopenia (50% vs. 8%), and anemia (32% vs. 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies. |
| References: | Blood Cancer J. 2018 Nov 9;8(11):109. (PMID: 30413684) Lancet Oncol. 2021 Jun;22(6):801-812. (PMID: 34087126) Lancet. 2016 Apr 9;387(10027):1551-1560. (PMID: 26778538) Cancer Treat Rev. 2021 Nov;100:102284. (PMID: 34597912) Br J Haematol. 2021 Apr;193(1):101-112. (PMID: 33368165) N Engl J Med. 2015 Sep 24;373(13):1207-19. (PMID: 26308596) Haematologica. 2019 Jul;104(7):1440-1450. (PMID: 30733268) Leukemia. 2017 Nov;31(11):2443-2448. (PMID: 28620163) Lancet Haematol. 2020 May;7(5):e395-e407. (PMID: 32213344) N Engl J Med. 2018 Feb 8;378(6):518-528. (PMID: 29231133) Lancet Haematol. 2022 Feb;9(2):e98-e110. (PMID: 35032434) BMC Cancer. 2021 Nov 12;21(1):1207. (PMID: 34772368) Oncotarget. 2017 Jun 8;8(39):66641-66655. (PMID: 29029544) Blood. 2016 Jul 7;128(1):37-44. (PMID: 27216216) Am J Hematol. 2022 Aug;97(8):1086-1107. (PMID: 35560063) Br J Haematol. 2016 Aug;174(3):397-409. (PMID: 27098276) Int J Hematol. 2019 Nov;110(5):559-565. (PMID: 31392600) Nat Rev Dis Primers. 2017 Jul 20;3:17046. (PMID: 28726797) Clin Cancer Res. 2013 Jun 1;19(11):3019-31. (PMID: 23584492) Front Oncol. 2021 Feb 15;10:575168. (PMID: 33659205) Lancet. 2019 Dec 7;394(10214):2096-2107. (PMID: 31735560) J Drug Target. 2003 Jul;11(6):355-63. (PMID: 14668056) PLoS One. 2021 Oct 13;16(10):e0258487. (PMID: 34644367) Haematologica. 2022 Oct 01;107(10):2408-2417. (PMID: 35354247) Blood. 2011 May 5;117(18):4691-5. (PMID: 21292775) Biochem Pharmacol. 2010 May 1;79(9):1281-90. (PMID: 20067771) EJHaem. 2020 Nov 08;2(1):56-65. (PMID: 35846104) J Clin Oncol. 2021 Mar 1;39(7):757-767. (PMID: 33296242) Blood. 2017 Aug 24;130(8):974-981. (PMID: 28637662) N Engl J Med. 2016 Oct 6;375(14):1319-1331. (PMID: 27705267) Oncol Res. 2003;14(3):113-32. (PMID: 14760861) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT04649060 |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 4Z63YK6E0E (daratumumab) 7S5I7G3JQL (Dexamethasone) 3412470A0V (melflufen) Q41OR9510P (Melphalan) 47E5O17Y3R (Phenylalanine) 0 (Proteasome Inhibitors) |
| تواريخ الأحداث: | Date Created: 20230830 Date Completed: 20240304 Latest Revision: 20240816 |
| رمز التحديث: | 20240816 |
| مُعرف محوري في PubMed: | PMC10905085 |
| DOI: | 10.3324/haematol.2023.283509 |
| PMID: | 37646660 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1592-8721 |
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| DOI: | 10.3324/haematol.2023.283509 |