In patients with multiple myeloma, the combination of motixafortide and granulocyte colony-stimulating factor achieved a 4.9-fold increase in hematopoietic stem-cell mobilization, and prepared most patients for autologous stem cell transplant, meeting both the primary and main secondary endpoints of the GENESIS Study.
In patients with multiple myeloma, the combination of motixafortide (BL-8040) and granulocyte colony-stimulating factor (G-CSF) achieved a 4.9-fold increase in hematopoietic stem-cell mobilization, and prepared most patients for autologous stem cell transplant (ASCT), meeting both the primary and main secondary endpoints of the GENESIS Study (NCT03246529), according to a press release by BioLineRx Ltd.
Motixafortide is meant to target CDCR4, a chemokine receptor that is overexpressed in many cancers, including pancreatic cancer. In addition to multiple myeloma, the agent is being investigated in solid tumors and acute myeloid leukemia.2
The randomized, parallel assignment, phase 3 GENESIS study aims to enroll 207 patients. The primary outcome of the study is the percentage of participants mobilizing ≥ 6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions. Secondary endpoints included the rate of patients who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session, the rate of patients who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session, time to neutrophil engraftment, time to platelet engraftment, and graft durability at 100 days post engraftment.
Patients were randomized 2:1 into 1 of 2 arms. During the experimental arm, patients received motixafortide and G-CSF. In the comparator arm, patients received a placebo in place of motixafortide.
In order to participate, patients must have histologically confirmed multiple myeloma, at least 4 weeks from last induction cycle of chemotherapy, eligible for hematopoietic stem cell transplantation, in their first or second complete remission, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function at baseline, and using effective contraception. Patients with a previous history of autologous or allogeneic-HCT failed previous HSC collections or collection attempts, or who have received more than 6 cycles of lifetime exposure to lenalidomide are not eligible to participate.
In total, 122 people were enrolled. A data analysis found that the percentage of patients with mobilization of ≥ 6 million CD34+ cells/kg in up to 2 apheresis sessions in experimental arm was higher than the placebo arm at 70% compared with 14.3%, respectively(95% CI, 39.7%-69.5%; P <.0001), translating to a 12.9 odds-ratio.
A key secondary endpoint of the study was also reached. A 14.1-fold increase was seen between the treatment arm and the control arm in the rate of patients who mobilized ≥ 6 million CD34+ cells/kg in just 1 apheresis session. The rate of mobilization after just 1 apheresis session in the treatment arm was 67.5% compared with 4.8% in the comparator arm, translating to a 56.0 odds ratio.
In the treatment arm, 88.3% of patients were able to undergo transplantation after only one apheresis session compared to 10.8% in the placebo arm, amounting to an 8.2-fold increase. Additionally, data on the median number of CD34+ cells collected on the first day of apheresis was collected. In the treatment arm, the median was 8.5 million in the experimental arm versus 1.5 million in the control arm.
"The results of the GENESIS study are extremely impressive, and all the more so when considering that almost 90% of the patients in the treatment arm proceeded to transplantation after only one apheresis session," said John DiPersio, MD, the lead investigator of the study and professor at the Washington University School of Medicine, in a press release. "This is a great achievement in alleviating the burden for the patients and reducing hospital resources. I believe these results make the combination of Motixafortide and G-CSF a very attractive candidate for use in all patients with multiple myeloma undergoing ASCT."