Journal Article

Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial

Illes Arpad, Giulio A. Milone, Ella Sorani, Michael P. Rettig, Reyka G. Jayasinghe, Sarah M. Larson, John Hiemenz, Udo Holtick, Muzaffar H. Qazilbash, Ravi Vij, Patrick Stiff, Nancy Hardy, Abi Vainstein-Haras, Shaul Kadosh, Massimo Martino, Maria Liz Paciello Coronel, Zachary D. Crees, Irit Gliko-Kabir, Debby Ickowicz, Liron Shemesh-Darvish, John F. DiPersio, Gabor Mikala, Gemma Moreno-Jiménez, Tahir Latif, Mark A. Schroeder, Keith Stockerl-Goldstein, Ivana Micallef, Douglas Sborov, Irene García-Cadenas, Feng Gao, Denise Pereira, Inbal Goldstein

2023

Overview

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 The phase 3 GENESIS trial reports the superiority of the novel CXCR4 inhibitor motixafortide with G-CSF in mobilizing hematopoietic progenitor cells for autologous stem cell transplantation in multiple myeloma.

• Publisher: Springer Science and Business Media LLC,Nature Publishing Group US,Nature Publishing Group
• Subject: 631/532/1542 / 631/532/2063 / 631/67/1990/804 / 692/308/2171 / 692/308/2779/777 / Adult / Antigens / Antigens, CD34 / Antigens, CD34 - metabolism / Apheresis / Autografts / Autologous / Biomedical and Life Sciences / Biomedicine / Cancer Research / CD34 / CD34 antigen / Cell survival / Colony-stimulating factor / CXCR4 protein / Erythema / Granulocyte Colony-Stimulating Factor / Granulocyte Colony-Stimulating Factor - pharmacology / Granulocyte Colony-Stimulating Factor - therapeutic use / Hematopoietic Stem Cell Mobilization / Hematopoietic Stem Cell Mobilization - methods / Hematopoietic Stem Cell Transplantation / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic Stem Cells / Hematopoietic Stem Cells - metabolism / Heterocyclic Compounds / Heterocyclic Compounds - pharmacology / Heterocyclic Compounds - therapeutic use / Humans / ICTS (Institute of Clinical and Translational Sciences) / Immunologic Factors / Immunologic Factors - therapeutic use / Infectious Diseases / Inhibitors / Leukocytes (granulocytic) / Medicine and Health Sciences / Metabolic Diseases / Molecular Medicine / Multiple Myeloma / Multiple Myeloma - drug therapy / Neurosciences / Placebos / Progenitor cells / Prospective Studies / Stem cell transplantation / Stem cells / Transplantation / Transplantation, Autologous