| Autor: |
Spicka I; Department of Medicine, Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic., Ocio EM; Department of Hematology, University Hospital Marqués de Valdecilla/IDIVAL, University of Cantabria, Santander, Spain., Oakervee HE; Department of Haemato-Oncology, St Bartholomew's Cancer Centre, Barts Health NHS Trust, London, UK., Greil R; 3rd Medical Department, Paracelsus Medical University Salzburg, Salzburg Cancer Research Institute, Cancer Cluster Salzburg, Salzburg, Austria., Banh RH; Department of Clinical Haematology, Mater Health Services, Brisbane, Australia., Huang SY; Department of Medicine, National Taiwan University Hospital, Taipei, Taiwan., D'Rozario JM; Department of Hematology, Canberra Hospital and Health Service, Canberra, Australia., Dimopoulos MA; Department of Clinical Therapeutics, Alexandra General Hospital, Athens, Greece., Martínez S; Clinical R&D, Pharma Mar, Colmenar Viejo, Madrid, Spain., Extremera S; Clinical R&D, Pharma Mar, Colmenar Viejo, Madrid, Spain., Kahatt C; Clinical R&D, Pharma Mar, Colmenar Viejo, Madrid, Spain., Alfaro V; Clinical R&D, Pharma Mar, Colmenar Viejo, Madrid, Spain., Carella AM; Department of Hematology, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy., Meuleman N; Department of Hematology, Institut Jules Bordet (ULB), Brussels, Belgium., Hájek R; Department of Hematology-Oncology, Faculty of Medicine, University Hospital Ostrava, Ostrava, Czech Republic., Symeonidis A; Hematology Division, Department of Internal Medicine, University of Patras Medical School, Patras, Greece., Min CK; Department of Blood and Marrow Transplantation, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea., Cannell P; Department of Medicine, Royal Perth Hospital, Perth, Australia., Ludwig H; Wilhelminen Cancer Research Institute, Department of Medicine, Center for Oncology, Hematology and Palliative Care, Wilhelminen Hospital, Vienna, Austria., Sonneveld P; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Mateos MV; Department of Hematology, University Hospital of Salamanca/IBSAL, Salamanca, Spain. mvmateos@usal.es.; Departamento de Hematología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. mvmateos@usal.es. |
| Abstrakt: |
The randomized phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma after at least three but not more than six prior regimens, including at least bortezomib and lenalidomide or thalidomide. Patients were randomly assigned (2:1) to receive plitidepsin 5 mg/m 2 on D1 and D15 plus DXM 40 mg on D1, D8, D15, and D22 (arm A, n = 171) or DXM 40 mg on D1, D8, D15, and D22 (arm B, n = 84) q4wk. The primary endpoint was progression-free survival (PFS). Median PFS without disease progression (PD) confirmation (IRC assessment) was 2.6 months (arm A) and 1.7 months (arm B) (HR = 0.650; p = 0.0054). Median PFS with PD confirmation (investigator's assessment) was 3.8 months (arm A) and 1.9 months (arm B) (HR = 0.611; p = 0.0040). Median overall survival (OS, intention-to-treat analysis) was 11.6 months (arm A) and 8.9 months (arm B) (HR = 0.797; p = 0.1261). OS improvement favoring arm A was found when discounting a crossover effect (37 patients crossed over from arm B to arm A) (two-stage method; HR = 0.622; p = 0.0015). The most common grade 3/4 treatment-related adverse events (% of patients arm A/arm B) were fatigue (10.8%/1.2%), myalgia (5.4%/0%), and nausea (3.6%/1.2%), being usually transient and reversible. The safety profile does not overlap with the toxicity observed with other agents used in multiple myeloma. In conclusion, efficacy data, the reassuring safety profile, and the novel mechanism of action of plitidepsin suggest that this combination can be an alternative option in patients with relapsed/refractory multiple myeloma after at least three prior therapy lines. |
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