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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Friday, July 21, 2023
The CXCR4 inhibitor motixafortide, in combination with granulocyte colony–stimulating factor (G-CSF), may mobilize significantly more CD34-positive hematopoietic stem and progenitor cells within two apheresis procedures versus G-CSF alone, in preparation for autologous stem cell transplantation (ASCT), according to results of the phase III GENESIS trial. The study involved 122 adults with multiple myeloma in five countries, reported Zachary D. Crees, MD, of Washington University School of Medicine, St. Louis, and colleagues in Nature Medicine. The use of motixafortide also preferentially mobilized increased numbers of immunophenotypically and transcriptionally primitive hematopoietic stem and progenitor cells, they noted.
G-CSF mobilization alone often does not allow the optimal number of CD34-positive hematopoietic stem and progenitor cells to be collected prior to ASCT. The combination “enabled 92.5% [of patients] to successfully meet the primary endpoint [of collecting ≥ 6 × 106 CD34-positive cells kg–1 within two apheresis procedures] versus 26.2% with placebo plus G-CSF (P < .0001),” the team related. The patients were randomly assigned 2:1 to the investigative and control arms in this double-blind trial.
Motixafortide plus G-CSF also enabled 88.8% of patients to meet the secondary endpoint, of achieving the CD34-positive cell goal in one apheresis, versus 9.5% with placebo plus G-CSF (P < .0001). Further, according to the investigators, the combination was both safe and well tolerated; the most common treatment-emergent adverse events were transient grade 1 or 2 injection-site reactions.
“Future studies may consider similar regimens for hematopoietic stem and progenitor cell–based, gene-edited platforms where the optimal hematopoietic stem and progenitor cells collection goal is typically much higher (10–15 × 106 CD34-positive cells kg–1) than that of ASCT (5–6 × 106 CD34-positive cells kg–1), given losses of hematopoietic stem and progenitor cell viability–associated gene/base editing,” Dr. Crees and co-investigators suggested.
Disclosure: The study authors’ disclosure information can be found at nature.com.
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