Multicenter Long-Term Follow-Up of Allogeneic Hematopoietic Cell Transplantation with Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials

Abstract

Omidubicel is an umbilical cord blood (UCB)-derived ex vivo-expanded cellular therapy product that has demonstrated faster engraftment and fewer infections compared with unmanipulated UCB in allogeneic hematopoietic cell transplantation. Although the early benefits of omidubicel have been established, long-term outcomes remain unknown. We report on a planned pooled analysis of 5 multicenter clinical trials including 105 patients with hematologic malignancies or sickle cell hemoglobinopathy who underwent omidubicel transplantation at 26 academic transplantation centers worldwide. With a median follow-up of 22 months (range, .3 to 122 months), the 3-year estimated overall survival and disease-free survival were 62.5% and 54.0%, respectively. With up to 10 years of follow-up, omidubicel showed durable trilineage hematopoiesis. Serial quantitative assessments of CD3⁺, CD4⁺, CD8⁺, CD19⁺, CD116⁺CD56⁺, and CD123⁺ immune subsets revealed median counts remaining within normal ranges through up to 8 years of follow-up. Secondary graft failure occurred in 5 patients (5%) in the first year, with no late cases reported. One case of donor-derived myeloid neoplasm was reported at 40 months post-transplantation. This was also observed in a control arm patient who received only unmanipulated UCB. Overall, omidubicel demonstrated stable trilineage hematopoiesis, immune competence, and graft durability in extended follow-up.

Keywords: Allogeneic stem cell transplantation; Clinical trial; Cord blood; Ex vivo expansion; Long-term follow-up.

Figure 1.

Tukey box and whisker plots depicting trends of trilineage hematopoiesis and immune competence at up to 8–10 years post-transplant. A-C. Omidubicel demonstrates durable trilineage hematopoiesis over long-term follow-up. D-I. median counts of immune subsets fell within the normal range beginning at 1 year (early post-transplant immune reconstitution data not shown). Whiskers extend to the farthest points not considered outliers (1.5x the interquartile range from the median). Outliers are indicated by individual data points, while asterisk (*) indicate additional outlier points beyond the range of the figure. The lower limit of normal for various immune subsets are indicated by the dotted line, where available. WBC: white blood cells, NK cells: natural killer cells.

Figure 2.

Survival analyses and cumulative incidence estimates among all included patients (N = 105). A, B. Kaplan-Meier survival curves depicting overall survival and disease-free survival in all patients. C, D. Competing risk analyses estimating the cumulative incidences of chronic GVHD and disease relapse in all included patients. The competing risks for chronic GVHD were death from any cause, disease relapse, and graft failure. The competing risks for disease relapse were death from any cause and graft failure. cGVHD: chronic graft-versus-host disease, CI: confidence interval. OS: overall survival, DFS: disease-free survival, CI: confidence interval.