Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.
Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.
复制标题
DOI：
10.1038/s41591-023-02273-z
复制
发表时间：
2023-04
期刊：
影响因子：
82.9
通讯作者：
DiPersio, John F.
中科院分区：
文献类型：
--
作者：
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-Jimenez, Gemma;Mikala, Gabor;Coronel, Maria Liz Paciello;Holtick, Udo;Hiemenz, John;Qazilbash, Muzaffar H.;Hardy, Nancy;Latif, Tahir;Garcia-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.
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 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.
登录
查看更多内容
影响因子：
10.1
作者：
Lagresle-Peyrou C;Lefrère F;Magrin E;Ribeil JA;Romano O;Weber L;Magnani A;Sadek H;Plantier C;Gabrion A;Ternaux B;Félix T;Couzin C;Stanislas A;Tréluyer JM;Lamhaut L;Joseph L;Delville M;Miccio A;André-Schmutz I;Cavazzana M
通讯作者：
Cavazzana M
影响因子：
2.9
作者：
Choi, Hye-Yoon;Yong, Chul-Soon;Yoo, Bong Kyu
通讯作者：
Yoo, Bong Kyu
影响因子：
2.6
作者：
Hay SB;Ferchen K;Chetal K;Grimes HL;Salomonis N
通讯作者：
Salomonis N
影响因子：
45.3
作者：
Fermand, J;Katsahian, S;Ravaud, P
通讯作者：
Ravaud, P
影响因子：
3.3
作者：
Crees, Zachary D.;Stockerl-Goldstein, Keith;DiPersio, John F.
通讯作者：
DiPersio, John F.