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, Zachary D., Rettig, Michael P., Jayasinghe, Reyka G., Stockerl-Goldstein, Keith, Larson, Sarah M., Arpad, Illes, Milone, Giulio A., Martino, Massimo, Stiff, Patrick, Sborov, Douglas, Pereira, Denise, Micallef, Ivana, Moreno-Jiménez, Gemma, Mikala, Gabor, Coronel, Maria Liz Paciello, Holtick, Udo, Hiemenz, John, Qazilbash, Muzaffar H., Hardy, Nancy, Latif, Tahir, García-Cadenas, Irene, Vainstein-Haras, Abi, Sorani, Ella, Gliko-Kabir, Irit, Goldstein, Inbal, Ickowicz, Debby, Shemesh-Darvish, Liron, Kadosh, Shaul, Gao, Feng, Schroeder, Mark A., Vij, Ravi, DiPersio, John F. |
| المساهمون: | U.S. Department of Health & Human Services | National Institutes of Health, U.S. Department of Health & Human Services | NIH | National Cancer Institute |
| المصدر: | Nature Medicine ; volume 29, issue 4, page 869-879 ; ISSN 1078-8956 1546-170X |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Biochemistry, Genetics and Molecular Biology, General Medicine |
| الوصف: | 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 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41591-023-02273-z |
| الإتاحة: | https://doi.org/10.1038/s41591-023-02273-zTest https://www.nature.com/articles/s41591-023-02273-z.pdfTest https://www.nature.com/articles/s41591-023-02273-zTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.FF960E17 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41591-023-02273-z |
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