Omidubicel, an investigational enriched umbilical cord blood product being developed by Gamida Cell for transplantation in patients with blood cancers, appears to have some advantages over standard umbilical cord blood.
The results come from a global phase 3 trial (NCT02730299) presented at the annual meeting of the European Society for Blood and Bone Marrow Transplantation.
“Transplantation with omidubicel compared to standard cord blood transplantation results in faster hematopoietic recovery, fewer infections, and fewer days in hospital,” said coinvestigator Guillermo F. Sanz, MD, PhD, from the Hospital Universitari i Politècnic la Fe in Valencia, Spain.
“Omidubicel should be considered as the new standard of care for patients eligible for umbilical cord blood transplantation,” Sanz concluded.
Zachariah DeFilipp, MD, from the Massachusetts General Cancer Center in Boston, a hematopoietic stem cell transplantation specialist, was not involved in the study and was approached for comment. He told Medscape Medical News that “omidubicel significantly improves the engraftment after transplant, as compared to standard cord blood transplant. For patients that lack an HLA-matched donor, this approach can help overcome the prolonged cytopenias that occur with standard cord blood transplants in adults.”
Gamida Cell plans to submit these data for approval of omidubicel by the US Food and Drug Administration in the fourth quarter of 2021.
Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937).
Although umbilical cord blood stem cell grafts come from a readily available source and show greater tolerance across HLA barriers than other sources (such as bone marrow), the relatively low dose of stem cells in each unit results in delayed hematopoietic recovery, increased transplant-related morbidity and mortality, and longer hospitalizations, Sanz said.
Omidubicel consists of two cryopreserved fractions from a single cord blood unit. The product contains both noncultured CD133-negative cells, including T cells, and CD133-positive cells that are then expanded ex vivo for 21 days in the presence of nicotinamide.
“Nicotinamide increases stem and progenitor cells, inhibits differentiation and increases migration, bone marrow homing, and engraftment efficiency while preserving cellular functionality and phenotype,” Sanz explained during his presentation.
In an earlier phase 1/2 trial in 36 patients with high-risk hematologic malignancies, omidubicel was associated with hematopoietic engraftment lasting at least 10 years.
Details of Phase 3 Trial Results
The global phase 3 trial was conducted in 125 patients (aged 13-65) with high-risk malignancies, including acute myeloid and lymphoblastic leukemias, myelodysplastic syndrome, chronic myeloid leukemia, lymphomas, and rare leukemias. These patients were all eligible for allogeneic stem cell transplantation but did not have matched donors.
Patients were randomly assigned to receive hematopoietic reconstitution with either omidubicel (n = 52) or standard cord blood (58).
At 42 days of follow-up, the median time to neutrophil engraftment in the intention-to-treat (ITT) population, the primary endpoint, was 12 days with omidubicel versus 22 days with standard cord blood (P < .001).
In the as-treated population — the 108 patients who actually received omidubicel or standard cord blood — median time to engraftment was 10.0 versus 20.5 days, respectively (P < .001).
Rates of neutrophil engraftment at 42 days were 96% with omidubicel versus 89% with standard cord blood.
The secondary endpoint of time-to-platelet engraftment in the ITT population also favored omidubicel, with a cumulative day 42 incidence rate of 55% compared with 35% with standard cord blood (P = .028).
In the as-treated population, median times to platelet engraftment were 37 days and 50 days, respectively (P = .023). The cumulative rates of platelet engraftment at 100 days of follow-up were 83% and 73%, respectively.
The incidence of grade 2 or 3 bacterial or invasive fungal infections by day 100 in the ITT population was 37% among patients who received omidubicel, compared with 57% for patients who received standard cord blood (P = .027). Viral infections occurred in 10% versus 26% of patients, respectively.
The incidence of acute graft versus host disease at day 100 was similar between treatment groups, and there was no significant difference at 1 year.
Relapse and nonrelapse mortality rates, as well as disease-free and overall survival rates also did not differ between groups.
In the first 100 days post-transplant, patients who received omidubicel were alive and out of the hospital for a median of 60.5 days, compared with 48 days for patients who received standard cord blood (P = .005).
The study was funded by Gamida Cell. Sanz has reported receiving research funding from the company and several others, and consulting fees, honoraria, speakers bureau activity and travel expenses from other companies. DeFilipp has reported no relevant financial relationships.
EBMT 2021. Abstract GS2-7. Presented March 15, 2021.