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

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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:,

Original languageEnglish
Pages (from-to)869-879
Number of pages11
JournalNature medicine
Issue number4
StatePublished - Apr 2023


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