TY - JOUR
T1 - Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma
T2 - a randomized phase 3 trial
AU - Crees, Zachary D.
AU - Rettig, Michael P.
AU - Jayasinghe, Reyka G.
AU - Stockerl-Goldstein, Keith
AU - Larson, Sarah M.
AU - Arpad, Illes
AU - Milone, Giulio A.
AU - Martino, Massimo
AU - Stiff, Patrick
AU - Sborov, Douglas
AU - Pereira, Denise
AU - Micallef, Ivana
AU - Moreno-Jiménez, Gemma
AU - Mikala, Gabor
AU - Coronel, Maria Liz Paciello
AU - Holtick, Udo
AU - Hiemenz, John
AU - Qazilbash, Muzaffar H.
AU - Hardy, Nancy
AU - Latif, Tahir
AU - García-Cadenas, Irene
AU - Vainstein-Haras, Abi
AU - Sorani, Ella
AU - Gliko-Kabir, Irit
AU - Goldstein, Inbal
AU - Ickowicz, Debby
AU - Shemesh-Darvish, Liron
AU - Kadosh, Shaul
AU - Gao, Feng
AU - Schroeder, Mark A.
AU - Vij, Ravi
AU - DiPersio, John F.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4
Y1 - 2023/4
N2 - 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,
AB - 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,
UR - http://www.scopus.com/inward/record.url?scp=85153100489&partnerID=8YFLogxK
U2 - 10.1038/s41591-023-02273-z
DO - 10.1038/s41591-023-02273-z
M3 - Article
C2 - 37069359
AN - SCOPUS:85153100489
SN - 1078-8956
VL - 29
SP - 869
EP - 879
JO - Nature medicine
JF - Nature medicine
IS - 4
ER -