Nature medicine · 2023
Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.
Клиническое исследование III фазыРандомизированное исследованиеМногоцентровое исследованиеСтатьяПоддержка NIH: внешняя программаEquivalence TrialНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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 × 106 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.