Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma : a randomized phase 3 trial
Crees, Zachary D. (Washington University School of Medicine in St. Louis)
Rettig, Michael P. (Washington University School of Medicine in St. Louis)
Jayasinghe, Reyka (Washington University School of Medicine in St. Louis)
Stockerl-Goldstein, Keith (Washington University School of Medicine in St. Louis)
Larson, Sarah M. (University of California Los Angeles School. of Medicine)
Arpad, Illes (University of Debrecen)
Milone, Giulio A. (Azienda Ospedaliero Universitaria 'Policlinico-San Marco')
Martino, Massimo (Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli)
Stiff, Patrick (Loyola University Medical Center)
Sborov, Douglas (University of Utah School of Medicine)
Pereira, Denise (University of Miami Health System)
Micallef, Ivana (Mayo Clinic (Rochester, Estats Units d'Amèrica))
Moreno-Jiménez, Gemma (Hospital Universitario Ramón y Cajal (Madrid))
Mikala, Gabor (National Institute of Hematology and Infectious Diseases)
Paciello Coronel, Maria Liz (Hospital Universitario 12 de Octubre (Madrid))
Holtick, Udo (University of Cologne)
Hiemenz, John (University of Florida)
Qazilbash, Muzaffar H. (University of Texas MD Anderson Cancer Center)
Hardy, Nancy (University of Maryland School of Medicine)
Latif, Tahir (University of Cincinnati)
Garcia Cadenas, Irene (Institut d'Investigació Biomèdica Sant Pau)
Vainstein-Haras, Abi (BioLineRx. Ltd.)
Sorani, Ella (BioLineRx. Ltd.)
Gliko-Kabir, Irit (BioLineRx. Ltd.)
Goldstein, Inbal (BioLineRx. Ltd.)
Ickowicz, Debby (BioLineRx. Ltd.)
Shemesh-Darvish, Liron (BioLineRx. Ltd.)
Kadosh, Shaul (StatExcellence. Ltd.)
Gao, Feng (Washington University School of Medicine in St. Louis)
Schroeder, Mark A. (Washington University School of Medicine in St. Louis)
Vij, Ravi (Washington University School of Medicine in St. Louis)
DiPersio, John (Washington University School of Medicine in St. Louis)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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 CD34 cells kg 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. ClinicalTrials. gov, NCT03246529.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Nature Medicine, Vol. 29 Núm. 4 (april 2023) , p. 869-879, ISSN 1546-170X

DOI: 10.1038/s41591-023-02273-z
PMID: 37069359

32 p, 15.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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