دورية أكاديمية
Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.
| العنوان: | Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. |
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| المؤلفون: | Crees ZD; Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA. zcrees@wustl.edu., Rettig MP; Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA., Jayasinghe RG; Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA., Stockerl-Goldstein K; Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA., Larson SM; Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, CA, USA., Arpad I; Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Milone GA; Unità di Trapianto Emopoietico, Azienda Ospedaliero Universitaria 'Policlinico-San Marco', Catania, Italy., Martino M; Unit of Stem Cell Transplantation and Cellular Therapies, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy., Stiff P; Loyola University Medical Center, Maywood, CA, USA., Sborov D; Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA., Pereira D; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA., Micallef I; Division of Hematology, Mayo Clinic, Rochester, MN, USA., Moreno-Jiménez G; Department of Hematology, Ramon y Cajal University Hospital, Madrid, Spain., Mikala G; Center Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary., Coronel MLP; Hospital University 12 De Octubre, Madrid, Spain., Holtick U; Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne, University of Cologne, Cologne, Germany., Hiemenz J; Division of Hematology-Oncology, University of Florida, Gainesville, FL, USA., Qazilbash MH; Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hardy N; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA., Latif T; Division of Hematology-Oncology, University of Cincinnati, Cincinnati, OH, USA., García-Cadenas I; Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain., Vainstein-Haras A; BioLineRx, Ltd., Modi'in, Israel., Sorani E; BioLineRx, Ltd., Modi'in, Israel., Gliko-Kabir I; BioLineRx, Ltd., Modi'in, Israel., Goldstein I; BioLineRx, Ltd., Modi'in, Israel., Ickowicz D; BioLineRx, Ltd., Modi'in, Israel., Shemesh-Darvish L; BioLineRx, Ltd., Modi'in, Israel., Kadosh S; StatExcellence, Ltd., Kyriat Mozkin, Israel., Gao F; Division of Public Health Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, USA., Schroeder MA; Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA., Vij R; Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA., DiPersio JF; Division of Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA. |
| المصدر: | Nature medicine [Nat Med] 2023 Apr; Vol. 29 (4), pp. 869-879. Date of Electronic Publication: 2023 Apr 17. |
| نوع المنشور: | Clinical Trial, Phase III; Randomized Controlled Trial; Multicenter Study; Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Nature Publishing Company Original Publication: New York, NY : Nature Pub. Co., [1995- |
| مواضيع طبية MeSH: | Multiple Myeloma*/drug therapy , Heterocyclic Compounds*/pharmacology , Heterocyclic Compounds*/therapeutic use , Hematopoietic Stem Cell Transplantation*/adverse effects, Adult ; Humans ; Transplantation, Autologous ; Prospective Studies ; Hematopoietic Stem Cell Mobilization/methods ; Hematopoietic Stem Cells/metabolism ; Antigens, CD34/metabolism ; Granulocyte Colony-Stimulating Factor/pharmacology ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Immunologic Factors/therapeutic use |
| مستخلص: | Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34 + hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 10 6 CD34 + cells kg -1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12-201.33, P < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36-549.35, P < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34 + HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov , NCT03246529. (© 2023. The Author(s).) |
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| معلومات مُعتمدة: | P30 CA091842 United States CA NCI NIH HHS; R35 CA210084 United States CA NCI NIH HHS; R50 CA211466 United States CA NCI NIH HHS |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03246529 |
| المشرفين على المادة: | 0 (Heterocyclic Compounds) 0 (Antigens, CD34) 143011-72-7 (Granulocyte Colony-Stimulating Factor) 0 (Immunologic Factors) |
| تواريخ الأحداث: | Date Created: 20230417 Date Completed: 20230421 Latest Revision: 20240425 |
| رمز التحديث: | 20240425 |
| مُعرف محوري في PubMed: | PMC10115633 |
| DOI: | 10.1038/s41591-023-02273-z |
| PMID: | 37069359 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1546-170X |
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| DOI: | 10.1038/s41591-023-02273-z |